Transcription factor

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Transcription factor glossary
transcription – the process of making RNA from a DNA template by RNA polymerase
factor – a substance, such as a protein, that contributes to the cause of a specific biochemical reaction or bodily process
transcriptional regulationcontrolling the rate of gene transcription for example by helping or hindering RNA polymerase binding to DNA
upregulation, activation, or promotionincrease the rate of gene transcription
downregulation, repression, or suppressiondecrease the rate of gene transcription
coactivator – a protein that works with transcription factors to increase the rate of gene transcription
corepressor – a protein that works with transcription factors to decrease the rate of gene transcription
edit
Illustration of an activator

In molecular biology and genetics, a transcription factor (sometimes called a sequence-specific DNA-binding factor) is a protein that binds to specific DNA sequences, thereby controlling the rate of transcription of genetic information from DNA to messenger RNA.[1][2] Transcription factors perform this function alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA polymerase (the enzyme that performs the transcription of genetic information from DNA to RNA) to specific genes.[3][4][5]

A defining feature of transcription factors is that they contain one or more DNA-binding domains (DBDs), which attach to specific sequences of DNA adjacent to the genes that they regulate.[6][7] Additional proteins such as coactivators, chromatin remodelers, histone acetylases, deacetylases, kinases, and methylases, while also playing crucial roles in gene regulation, lack DNA-binding domains, and, therefore, are not classified as transcription factors.[8]

Conservation in different organisms[edit]

Transcription factors are essential for the regulation of gene expression and are, as a consequence, found in all living organisms. The number of transcription factors found within an organism increases with genome size, and larger genomes tend to have more transcription factors per gene.[9]

There are approximately 2600 proteins in the human genome that contain DNA-binding domains, and most of these are presumed to function as transcription factors.,[10] though other studies indicate it to be a smaller number.[11] Therefore, approximately 10% of genes in the genome code for transcription factors, which makes this family the single largest family of human proteins. Furthermore, genes are often flanked by several binding sites for distinct transcription factors, and efficient expression of each of these genes requires the cooperative action of several different transcription factors (see, for example, hepatocyte nuclear factors). Hence, the combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development.[8]


Mechanism[edit]

Transcription factors bind to either enhancer or promoter regions of DNA adjacent to the genes that they regulate. Depending on the transcription factor, the transcription of the adjacent gene is either up- or down-regulated. Transcription factors use a variety of mechanisms for the regulation of gene expression.[12] These mechanisms include:

  • stabilize or block the binding of RNA polymerase to DNA
  • catalyze the acetylation or deacetylation of histone proteins. The transcription factor can either do this directly or recruit other proteins with this catalytic activity. Many transcription factors use one or the other of two opposing mechanisms to regulate transcription:[13]
    • histone acetyltransferase (HAT) activity – acetylates histone proteins, which weakens the association of DNA with histones, which make the DNA more accessible to transcription, thereby up-regulating transcription
    • histone deacetylase (HDAC) activity – deacetylates histone proteins, which strengthens the association of DNA with histones, which make the DNA less accessible to transcription, thereby down-regulating transcription
  • recruit coactivator or corepressor proteins to the transcription factor DNA complex[14]

Function[edit]

Transcription factors are one of the groups of proteins that read and interpret the genetic "blueprint" in the DNA. They bind to the DNA and help initiate a program of increased or decreased gene transcription. As such, they are vital for many important cellular processes. Below are some of the important functions and biological roles transcription factors are involved in:

Basal transcription regulation[edit]

In eukaryotes, an important class of transcription factors called general transcription factors (GTFs) are necessary for transcription to occur.[15][16][17] Many of these GTFs don't actually bind DNA but are part of the large transcription preinitiation complex that interacts with RNA polymerase directly. The most common GTFs are TFIIA, TFIIB, TFIID (see also TATA binding protein), TFIIE, TFIIF, and TFIIH.[18] The preinitiation complex binds to promoter regions of DNA upstream to the gene that they regulate.

Differential enhancement of transcription[edit]

Other transcription factors differentially regulate the expression of various genes by binding to enhancer regions of DNA adjacent to regulated genes. These transcription factors are critical to making sure that genes are expressed in the right cell at the right time and in the right amount, depending on the changing requirements of the organism.

Development[edit]

Many transcription factors in multicellular organisms are involved in development.[19] Responding to cues (stimuli), these transcription factors turn on/off the transcription of the appropriate genes, which, in turn, allows for changes in cell morphology or activities needed for cell fate determination and cellular differentiation. The Hox transcription factor family, for example, is important for proper body pattern formation in organisms as diverse as fruit flies to humans.[20][21] Another example is the transcription factor encoded by the Sex-determining Region Y (SRY) gene, which plays a major role in determining sex in humans.[22]

Response to intercellular signals[edit]

Cells can communicate with each other by releasing molecules that produce signaling cascades within another receptive cell. If the signal requires upregulation or downregulation of genes in the recipient cell, often transcription factors will be downstream in the signaling cascade.[23] Estrogen signaling is an example of a fairly short signaling cascade that involves the estrogen receptor transcription factor: Estrogen is secreted by tissues such as the ovaries and placenta, crosses the cell membrane of the recipient cell, and is bound by the estrogen receptor in the cell's cytoplasm. The estrogen receptor then goes to the cell's nucleus and binds to its DNA-binding sites, changing the transcriptional regulation of the associated genes.[24]

Response to environment[edit]

Not only do transcription factors act downstream of signaling cascades related to biological stimuli but they can also be downstream of signaling cascades involved in environmental stimuli. Examples include heat shock factor (HSF), which upregulates genes necessary for survival at higher temperatures,[25] hypoxia inducible factor (HIF), which upregulates genes necessary for cell survival in low-oxygen environments,[26] and sterol regulatory element binding protein (SREBP), which helps maintain proper lipid levels in the cell.[27]

Cell cycle control[edit]

Many transcription factors, especially some that are proto-oncogenes or tumor suppressors, help regulate the cell cycle and as such determine how large a cell will get and when it can divide into two daughter cells.[28][29] One example is the Myc oncogene, which has important roles in cell growth and apoptosis.[30]

Pathogenesis[edit]

Transcription factors can also be used to alter gene expression in a host cell to promote pathogenesis. A well studied example of this are the transcription-activator like effectors (TAL effectors) secreted by Xanthomonas bacteria. When injected into plants, these proteins can enter the nucleus of the plant cell, bind plant promoter sequences, and activate transcription of plant genes that aid in bacterial infection.[31] TAL effectors contain a central repeat region in which there is a simple relationship between the identity of two critical residues in sequential repeats and sequential DNA bases in the TAL effector’s target site.[32][33] This property likely makes it easier for these proteins to evolve in order to better compete with the defense mechanisms of the host cell.[34]

Regulation[edit]

It is common in biology for important processes to have multiple layers of regulation and control. This is also true with transcription factors: Not only do transcription factors control the rates of transcription to regulate the amounts of gene products (RNA and protein) available to the cell but transcription factors themselves are regulated (often by other transcription factors). Below is a brief synopsis of some of the ways that the activity of transcription factors can be regulated:

Synthesis[edit]

Transcription factors (like all proteins) are transcribed from a gene on a chromosome into RNA, and then the RNA is translated into protein. Any of these steps can be regulated to affect the production (and thus activity) of a transcription factor. One interesting implication of this is that transcription factors can regulate themselves. For example, in a negative feedback loop, the transcription factor acts as its own repressor: If the transcription factor protein binds the DNA of its own gene, it will down-regulate the production of more of itself. This is one mechanism to maintain low levels of a transcription factor in a cell.

Nuclear localization[edit]

In eukaryotes, transcription factors (like most proteins) are transcribed in the nucleus but are then translated in the cell's cytoplasm. Many proteins that are active in the nucleus contain nuclear localization signals that direct them to the nucleus. But, for many transcription factors, this is a key point in their regulation.[35] Important classes of transcription factors such as some nuclear receptors must first bind a ligand while in the cytoplasm before they can relocate to the nucleus.[35]

Activation[edit]

Transcription factors may be activated (or deactivated) through their signal-sensing domain by a number of mechanisms including:

  • ligand binding – Not only is ligand binding able to influence where a transcription factor is located within a cell but ligand binding can also affect whether the transcription factor is in an active state and capable of binding DNA or other cofactors (see, for example, nuclear receptors).
  • phosphorylation[36][37] – Many transcription factors such as STAT proteins must be phosphorylated before they can bind DNA.
  • interaction with other transcription factors (e.g., homo- or hetero-dimerization) or coregulatory proteins

Accessibility of DNA-binding site[edit]

In eukaryotes, the DNA is organized with the help of histones in the compact particles, the nucleosomes, where about 147 DNA base pairs make ~1.65 turns around the histone protein octamer. DNA within nucleosomes is inaccessible to many transcription factors. Some transcription factors, so-called pioneering factors are still able to bind their DNA binding sites on the nucleosomal DNA. For most of other transcription factors, the nucleosome should be actively removed by molecular motors such as chromatin remodelers.[38] Alternatively, the nucleosome can be partially unwrapped by thermal fluctuations allowing temporary access to the transcription factor binding site. In many cases a transcription factor needs to compete for binding to its DNA binding site with other transcription factors and histones or non-histone chromatin proteins.[39] Pairs of transcription factors and other proteins can play antagonistic roles (activator versus repressor) in the regulation of the same gene.

Availability of other cofactors/transcription factors[edit]

Most transcription factors do not work alone. Often, for gene transcription to occur, a number of transcription factors must bind to DNA regulatory sequences. This collection of transcription factors, in turn, recruit intermediary proteins such as cofactors that allow efficient recruitment of the preinitiation complex and RNA polymerase. Thus, for a single transcription factor to initiate transcription, all of these other proteins must also be present, and the transcription factor must be in a state where it can bind to them if necessary. Cofactors are proteins that modulate the effects of transcription factors. Cofactors are interchangeable between specific gene promoters; depending on the protein complex that occupies the promoter DNA and the amino acid sequence of the cofactor, which determines its spatial conformation. As an example, certain steroid receptors can exchange cofactors with NF-κB, which is a switch between inflammation and cellular differentiation: thereby steroids can affect inflammatory response and function of certain tissues. [40]

Structure[edit]

Schematic diagram of the amino acid sequence (amino terminus to the left and carboxylic acid terminus to the right) of a prototypical transcription factor that contains (1) a DNA-binding domain (DBD), (2) signal-sensing domain (SSD), and a transactivation domain (TAD). The order of placement and the number of domains may differ in various types of transcription factors. In addition, the transactivation and signal-sensing functions are frequently contained within the same domain.

Transcription factors are modular in structure and contain the following domains:[1]

  • DNA-binding domain (DBD), which attach to specific sequences of DNA (enhancer or Promoter: Necessary component for all vectors: used to drive transcription of the vector's transgene promoter sequences) adjacent to regulated genes. DNA sequences that bind transcription factors are often referred to as response elements.
  • Trans-activating domain (TAD), which contain binding sites for other proteins such as transcription coregulators. These binding sites are frequently referred to as activation functions (AFs).[41]
  • An optional signal sensing domain (SSD) (e.g., a ligand binding domain), which senses external signals and, in response, transmits these signals to the rest of the transcription complex, resulting in up- or down-regulation of gene expression. Also, the DBD and signal-sensing domains may reside on separate proteins that associate within the transcription complex to regulate gene expression.

Trans-activating domain[edit]

Trans-activating domains (TADs) are named after their amino acid composition. These amino acids are either essential for the activity or simply the most abundant in the TAD. Transactivation by the Gal4 transcription factor is mediated by acidic amino acids, whereas hydrophobic residues in Gcn4 play a similar role. Hence, the TADs in Gal4 and Gcn4 are referred to as acidic or hydrophobic activation domains, respectively.[42]

Nine-amino-acid transactivation domain (9aaTAD) defines a novel domain common to a large superfamily of eukaryotic transcription factors represented by Gal4, Oaf1, Leu3, Rtg3, Pho4, Gln3, Gcn4 in yeast and by p53, NFAT, NF-κB and VP16 in mammals.[43]

9aaTAD transcription factors p53, VP16, MLL, E2A, HSF1, NF-IL6, NFAT1 and NF-κB interact directly with the general coactivators TAF9 and CBP/p300.[44] p53 9aaTADs interact with TAF9, GCN5 and with multiple domains of CBP/p300 (KIX, TAZ1,TAZ2 and IBiD).[45]

KIX domain of general coactivators Med15(Gal11) interacts with 9aaTAD transcription factors Gal4, Pdr1, Oaf1, Gcn4, VP16, Pho4, Msn2, Ino2 and P201.[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] Interactions of Gal4, Pdr1 and Gcn4 with Taf9 have been observed.[62][63][64] 9aaTAD is a common transactivation domain recruits multiple general coactivators TAF9, MED15, CBP/p300 and GCN5.[43]

Piskacek TF1.jpg

DNA-binding domain[edit]

Domain architecture example: Lactose Repressor (LacI). The N-terminal DNA binding domain (labeled) of lac repressor binds the its target DNA sequence (gold) in the major groove using a helix-turn-helix motif. Effector molecule binding (green) occurs in the core domain (labeled), a signal sensing domain. This triggers an allosteric response mediated by the linker region (labeled).
Main article: DNA-binding domain

The portion (domain) of the transcription factor that binds DNA is called its DNA-binding domain. Below is a partial list of some of the major families of DNA-binding domains/transcription factors:

Family InterPro Pfam SCOP
basic helix-loop-helix[65] IPR001092 Pfam PF00010 SCOP 47460
basic-leucine zipper (bZIP)[66] IPR004827 Pfam PF00170 SCOP 57959
C-terminal effector domain of the bipartite response regulators IPR001789 Pfam PF00072 SCOP 46894
GCC box SCOP 54175
helix-turn-helix[67]
homeodomain proteins - bind to homeobox DNA sequences, which in turn encode other transcription factors. Homeodomain proteins play critical roles in the regulation of development.[68] IPR009057 Pfam PF00046 SCOP 46689
lambda repressor-like IPR010982 SCOP 47413
srf-like (serum response factor) IPR002100 Pfam PF00319 SCOP 55455
paired box[69]
winged helix IPR013196 Pfam PF08279 SCOP 46785
zinc fingers[70]
* multi-domain Cys2His2 zinc fingers[71] IPR007087 Pfam PF00096 SCOP 57667
* Zn2/Cys6 SCOP 57701
* Zn2/Cys8 nuclear receptor zinc finger IPR001628 Pfam PF00105 SCOP 57716

Response elements[edit]

The DNA sequence that a transcription factor binds to is called a transcription factor-binding site or response element.[72]

Transcription factors interact with their binding sites using a combination of electrostatic (of which hydrogen bonds are a special case) and Van der Waals forces. Due to the nature of these chemical interactions, most transcription factors bind DNA in a sequence specific manner. However, not all bases in the transcription factor-binding site may actually interact with the transcription factor. In addition, some of these interactions may be weaker than others. Thus, transcription factors do not bind just one sequence but are capable of binding a subset of closely related sequences, each with a different strength of interaction.

For example, although the consensus binding site for the TATA-binding protein (TBP) is TATAAAA, the TBP transcription factor can also bind similar sequences such as TATATAT or TATATAA.

Because transcription factors can bind a set of related sequences and these sequences tend to be short, potential transcription factor binding sites can occur by chance if the DNA sequence is long enough. It is unlikely, however, that a transcription factor binds all compatible sequences in the genome of the cell. Other constraints, such as DNA accessibility in the cell or availability of cofactors may also help dictate where a transcription factor will actually bind. Thus, given the genome sequence it is still difficult to predict where a transcription factor will actually bind in a living cell.

Additional recognition specificity, however, may be obtained through the use of more than one DNA-binding domain (for example tandem DBDs in the same transcription factor or through dimerization of two transcription factors) that bind to two or more adjacent sequences of DNA.

Clinical significance[edit]

Transcription factors are of clinical significance for at least two reasons: (1) mutations can be associated with specific diseases, and (2) they can be targets of medications.

Disorders[edit]

Due to their important roles in development, intercellular signaling, and cell cycle, some human diseases have been associated with mutations in transcription factors.[73]

Many transcription factors are either tumor suppressors or oncogenes, and, thus, mutations or aberrant regulation of them is associated with cancer. Three groups of transcription factors are known to be important in human cancer: (1) the NF-kappaB and AP-1 families, (2) the STAT family and (3) the steroid receptors.[74]

Below are a few of the more well-studied examples:

Condition Description Locus
Rett syndrome Mutations in the MECP2 transcription factor are associated with Rett syndrome, a neurodevelopmental disorder.[75][76] Xq28
Diabetes A rare form of diabetes called MODY (Maturity onset diabetes of the young) can be caused by mutations in hepatocyte nuclear factors (HNFs)[77] or insulin promoter factor-1 (IPF1/Pdx1).[78] multiple
Developmental verbal dyspraxia Mutations in the FOXP2 transcription factor are associated with developmental verbal dyspraxia, a disease in which individuals are unable to produce the finely coordinated movements required for speech.[79] 7q31
Autoimmune diseases Mutations in the FOXP3 transcription factor cause a rare form of autoimmune disease called IPEX.[80] Xp11.23-q13.3
Li-Fraumeni syndrome Caused by mutations in the tumor suppressor p53.[81] 17p13.1
Breast cancer The STAT family is relevant to breast cancer.[82] multiple
Multiple cancers The HOX family are involved in a variety of cancers.[83] multiple

Potential drug targets[edit]

Approximately 10% of currently prescribed drugs directly target the nuclear receptor class of transcription factors.[84][not in citation given] Examples include tamoxifen and bicalutamide for the treatment of breast and prostate cancer, respectively, and various types of anti-inflammatory and anabolic steroids.[85] In addition, transcription factors are often indirectly modulated by drugs through signaling cascades. It might be possible to directly target other less-explored transcription factors such as NF-κB with drugs.[86][87][88][89] Transcription factors outside the nuclear receptor family are thought to be more difficult to target with small molecule therapeutics since it is not clear that they are "drugable" but progress has been made on the notch pathway.[90]

Role in Evolution[edit]

Gene duplications have played a crucial role in the evolution of species. This applies particularly to transcription factors. Once they occur as duplicates, accumulated mutations encoding for one copy can take place without negatively affecting the regulation of downstream targets. However, changes of the DNA binding specificities of the single-copy LEAFY transcription factor, which occurs in most land plants, have recently been elucidated. In that respect a single-copy transcription factor can undergo a change of specificity through a promiscuous intermediate without losing function. Similar mechanisms have been proposed in the context of all alternative phylogenetic hypotheses, and the role of transcription factors in the evolution of all species.[91]

Analysis[edit]

There are different technologies available to analyze transcription factors. On the genomic level, DNA-sequencing[92] and database research are commonly used[93][94] . The protein version of the transcription factor is detectable by using specific antibodies. The sample is detected on a western blot. By using electrophoretic mobility shift assay (EMSA),[95] the activation profile of transcription factors can be detected. A multiplex approach for activation profiling is a TF chip system where several of different transcription factors can be detected in parallel. This technology is based on DNA microarrays, providing the specific DNA-binding sequence for the transcription factor protein on the array surface.[96]

Classes[edit]

As described in more detail below, transcription factors may be classified by their (1) mechanism of action, (2) regulatory function, or (3) sequence homology (and hence structural similarity) in their DNA-binding domains.

Mechanistic[edit]

There are three mechanistic classes of transcription factors:

  • General transcription factors are involved in the formation of a preinitiation complex. The most common are abbreviated as TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. They are ubiquitous and interact with the core promoter region surrounding the transcription start site(s) of all class II genes.[97]
  • Upstream transcription factors are proteins that bind somewhere upstream of the initiation site to stimulate or repress transcription. These are roughly synonymous with specific transcription factors, because they vary considerably depending on what recognition sequences are present in the proximity of the gene.[98]
Examples of specific transcription factors[98]
Factor Structural type Recognition sequence Binds as
SP1 Zinc finger 5'-GGGCGG-3' Monomer
AP-1 Basic zipper 5'-TGA(G/C)TCA-3' Dimer
C/EBP Basic zipper 5'-ATTGCGCAAT-3' Dimer
Heat shock factor Basic zipper 5'-XGAAX-3' Trimer
ATF/CREB Basic zipper 5'-TGACGTCA-3' Dimer
c-Myc Basic helix-loop-helix 5'-CACGTG-3' Dimer
Oct-1 Helix-turn-helix 5'-ATGCAAAT-3' Monomer
NF-1 Novel 5'-TTGGCXXXXXGCCAA-3' Dimer
(G/C) = G or C
X = A, T, G or C

Functional[edit]

Transcription factors have been classified according to their regulatory function:[8]

  • I. constitutively active – present in all cells at all times – general transcription factors, Sp1, NF1, CCAAT
  • II. conditionally active – requires activation
    • II.A developmental (cell specific) – expression is tightly controlled, but, once expressed, require no additional activation – GATA, HNF, PIT-1, MyoD, Myf5, Hox, Winged Helix
    • II.B signal-dependent – requires external signal for activation
      • II.B.1 extracellular ligand (endocrine or paracrine)-dependentnuclear receptors
      • II.B.2 intracellular ligand (autocrine)-dependent - activated by small intracellular molecules – SREBP, p53, orphan nuclear receptors
      • II.B.3 cell membrane receptor-dependent – second messenger signaling cascades resulting in the phosphorylation of the transcription factor
        • II.B.3.a resident nuclear factors – reside in the nucleus regardless of activation state – CREB, AP-1, Mef2
        • II.B.3.b latent cytoplasmic factors – inactive form reside in the cytoplasm, but, when activated, are translocated into the nucleus – STAT, R-SMAD, NF-κB, Notch, TUBBY, NFAT

Structural[edit]

Transcription factors are often classified based on the sequence similarity and hence the tertiary structure of their DNA-binding domains:[99][100][101]

  • 1 Superclass: Basic Domains
    • 1.1 Class: Leucine zipper factors (bZIP)
      • 1.1.1 Family: AP-1(-like) components; includes (c-Fos/c-Jun)
      • 1.1.2 Family: CREB
      • 1.1.3 Family: C/EBP-like factors
      • 1.1.4 Family: bZIP / PAR
      • 1.1.5 Family: Plant G-box binding factors
      • 1.1.6 Family: ZIP only
    • 1.2 Class: Helix-loop-helix factors (bHLH)
      • 1.2.1 Family: Ubiquitous (class A) factors
      • 1.2.2 Family: Myogenic transcription factors (MyoD)
      • 1.2.3 Family: Achaete-Scute
      • 1.2.4 Family: Tal/Twist/Atonal/Hen
    • 1.3 Class: Helix-loop-helix / leucine zipper factors (bHLH-ZIP)
      • 1.3.1 Family: Ubiquitous bHLH-ZIP factors; includes USF (USF1, USF2); SREBP (SREBP)
      • 1.3.2 Family: Cell-cycle controlling factors; includes c-Myc
    • 1.4 Class: NF-1
      • 1.4.1 Family: NF-1 (A, B, C, X)
    • 1.5 Class: RF-X
      • 1.5.1 Family: RF-X (1, 2, 3, 4, 5, ANK)
    • 1.6 Class: bHSH
  • 2 Superclass: Zinc-coordinating DNA-binding domains
    • 2.1 Class: Cys4 zinc finger of nuclear receptor type
    • 2.2 Class: diverse Cys4 zinc fingers
    • 2.3 Class: Cys2His2 zinc finger domain
      • 2.3.1 Family: Ubiquitous factors, includes TFIIIA, Sp1
      • 2.3.2 Family: Developmental / cell cycle regulators; includes Krüppel
      • 2.3.4 Family: Large factors with NF-6B-like binding properties
    • 2.4 Class: Cys6 cysteine-zinc cluster
    • 2.5 Class: Zinc fingers of alternating composition
  • 3 Superclass: Helix-turn-helix
    • 3.1 Class: Homeo domain
      • 3.1.1 Family: Homeo domain only; includes Ubx
      • 3.1.2 Family: POU domain factors; includes Oct
      • 3.1.3 Family: Homeo domain with LIM region
      • 3.1.4 Family: homeo domain plus zinc finger motifs
    • 3.2 Class: Paired box
      • 3.2.1 Family: Paired plus homeo domain
      • 3.2.2 Family: Paired domain only
    • 3.3 Class: Fork head / winged helix
      • 3.3.1 Family: Developmental regulators; includes forkhead
      • 3.3.2 Family: Tissue-specific regulators
      • 3.3.3 Family: Cell-cycle controlling factors
      • 3.3.0 Family: Other regulators
    • 3.4 Class: Heat Shock Factors
      • 3.4.1 Family: HSF
    • 3.5 Class: Tryptophan clusters
    • 3.6 Class: TEA ( transcriptional enhancer factor) domain
  • 4 Superclass: beta-Scaffold Factors with Minor Groove Contacts
    • 4.1 Class: RHR (Rel homology region)
    • 4.2 Class: STAT
      • 4.2.1 Family: STAT
    • 4.3 Class: p53
      • 4.3.1 Family: p53
    • 4.4 Class: MADS box
      • 4.4.1 Family: Regulators of differentiation; includes (Mef2)
      • 4.4.2 Family: Responders to external signals, SRF (serum response factor) (SRF)
      • 4.4.3 Family: Metabolic regulators (ARG80)
    • 4.5 Class: beta-Barrel alpha-helix transcription factors
    • 4.6 Class: TATA binding proteins
      • 4.6.1 Family: TBP
    • 4.7 Class: HMG-box
      • 4.7.1 Family: SOX genes, SRY
      • 4.7.2 Family: TCF-1 (TCF1)
      • 4.7.3 Family: HMG2-related, SSRP1
      • 4.7.4 Family: UBF
      • 4.7.5 Family: MATA
    • 4.8 Class: Heteromeric CCAAT factors
      • 4.8.1 Family: Heteromeric CCAAT factors
    • 4.9 Class: Grainyhead
      • 4.9.1 Family: Grainyhead
    • 4.10 Class: Cold-shock domain factors
      • 4.10.1 Family: csd
    • 4.11 Class: Runt
      • 4.11.1 Family: Runt
  • 0 Superclass: Other Transcription Factors
    • 0.1 Class: Copper fist proteins
    • 0.2 Class: HMGI(Y) (HMGA1)
      • 0.2.1 Family: HMGI(Y)
    • 0.3 Class: Pocket domain
    • 0.4 Class: E1A-like factors
    • 0.5 Class: AP2/EREBP-related factors
      • 0.5.1 Family: AP2
      • 0.5.2 Family: EREBP
      • 0.5.3 Superfamily: AP2/B3
        • 0.5.3.1 Family: ARF
        • 0.5.3.2 Family: ABI
        • 0.5.3.3 Family: RAV

See also[edit]

References[edit]

  1. ^ a b Latchman DS (1997). "Transcription factors: an overview". Int. J. Biochem. Cell Biol. 29 (12): 1305–12. doi:10.1016/S1357-2725(97)00085-X. PMID 9570129. 
  2. ^ Karin M (1990). "Too many transcription factors: positive and negative interactions". New Biol. 2 (2): 126–31. PMID 2128034. 
  3. ^ Roeder RG (1996). "The role of general initiation factors in transcription by RNA polymerase II". Trends Biochem. Sci. 21 (9): 327–35. doi:10.1016/0968-0004(96)10050-5. PMID 8870495. 
  4. ^ Nikolov DB, Burley SK (1997). "RNA polymerase II transcription initiation: A structural view". Proc. Natl. Acad. Sci. U.S.A. 94 (1): 15–22. Bibcode:1997PNAS...94...15N. doi:10.1073/pnas.94.1.15. PMC 33652. PMID 8990153. 
  5. ^ Lee TI, Young RA (2000). "Transcription of eukaryotic protein-coding genes". Annu. Rev. Genet. 34: 77–137. doi:10.1146/annurev.genet.34.1.77. PMID 11092823. 
  6. ^ Mitchell PJ, Tjian R (1989). "Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins". Science 245 (4916): 371–8. Bibcode:1989Sci...245..371M. doi:10.1126/science.2667136. PMID 2667136. 
  7. ^ Ptashne M, Gann A (1997). "Transcriptional activation by recruitment". Nature 386 (6625): 569–77. Bibcode:1997Natur.386..569P. doi:10.1038/386569a0. PMID 9121580. 
  8. ^ a b c Brivanlou AH, Darnell JE (2002). "Signal transduction and the control of gene expression". Science 295 (5556): 813–8. Bibcode:2002Sci...295..813B. doi:10.1126/science.1066355. PMID 11823631. 
  9. ^ van Nimwegen E (2003). "Scaling laws in the functional content of genomes". Trends Genet. 19 (9): 479–84. doi:10.1016/S0168-9525(03)00203-8. PMID 12957540. 
  10. ^ Babu MM, Luscombe NM, Aravind L, Gerstein M, Teichmann SA (2004). "Structure and evolution of transcriptional regulatory networks". Curr. Opin. Struct. Biol. 14 (3): 283–91. doi:10.1016/j.sbi.2004.05.004. PMID 15193307. 
  11. ^ http://www.biostars.org/p/53590/
  12. ^ Gill G (2001). "Regulation of the initiation of eukaryotic transcription". Essays Biochem. 37: 33–43. PMID 11758455. 
  13. ^ Narlikar GJ, Fan HY, Kingston RE (February 2002). "Cooperation between complexes that regulate chromatin structure and transcription". Cell 108 (4): 475–87. doi:10.1016/S0092-8674(02)00654-2. PMID 11909519. 
  14. ^ Xu L, Glass CK, Rosenfeld MG (April 1999). "Coactivator and corepressor complexes in nuclear receptor function". Curr. Opin. Genet. Dev. 9 (2): 140–7. doi:10.1016/S0959-437X(99)80021-5. PMID 10322133. 
  15. ^ Robert O. J. Weinzierl (1999). Mechanisms of Gene Expression: Structure, Function and Evolution of the Basal Transcriptional Machinery. World Scientific Publishing Company. ISBN 1-86094-126-5. 
  16. ^ Reese JC (April 2003). "Basal transcription factors". Current opinion in genetics & development 13 (2): 114–8. doi:10.1016/S0959-437X(03)00013-3. PMID 12672487. 
  17. ^ Shilatifard A, Conaway RC, Conaway JW (2003). "The RNA polymerase II elongation complex". Annual review of biochemistry 72: 693–715. doi:10.1146/annurev.biochem.72.121801.161551. PMID 12676794. 
  18. ^ Thomas MC, Chiang CM (2006). "The general transcription machinery and general cofactors". Critical reviews in biochemistry and molecular biology 41 (3): 105–78. doi:10.1080/10409230600648736. PMID 16858867. 
  19. ^ Lobe CG (1992). "Transcription factors and mammalian development". Current topics in developmental biology. Current Topics in Developmental Biology 27: 351–83. doi:10.1016/S0070-2153(08)60539-6. ISBN 978-0-12-153127-0. PMID 1424766. 
  20. ^ Lemons D, McGinnis W (September 2006). "Genomic evolution of Hox gene clusters". Science 313 (5795): 1918–22. Bibcode:2006Sci...313.1918L. doi:10.1126/science.1132040. PMID 17008523. 
  21. ^ Moens CB, Selleri L (March 2006). "Hox cofactors in vertebrate development". Developmental biology 291 (2): 193–206. doi:10.1016/j.ydbio.2005.10.032. PMID 16515781. 
  22. ^ Ottolenghi C, Uda M, Crisponi L, Omari S, Cao A, Forabosco A, Schlessinger D (January 2007). "Determination and stability of sex". BioEssays : news and reviews in molecular, cellular and developmental biology 29 (1): 15–25. doi:10.1002/bies.20515. PMID 17187356. 
  23. ^ Pawson T (1993). "Signal transduction--a conserved pathway from the membrane to the nucleus". Developmental genetics 14 (5): 333–8. doi:10.1002/dvg.1020140502. PMID 8293575. 
  24. ^ Osborne CK, Schiff R, Fuqua SA, Shou J (December 2001). "Estrogen receptor: current understanding of its activation and modulation". Clin. Cancer Res. 7 (12 Suppl): 4338s–4342s; discussion 4411s–4412s. PMID 11916222. 
  25. ^ Shamovsky I, Nudler E (March 2008). "New insights into the mechanism of heat shock response activation". Cell. Mol. Life Sci. 65 (6): 855–61. doi:10.1007/s00018-008-7458-y. PMID 18239856. 
  26. ^ Benizri E, Ginouvès A, Berra E (April 2008). "The magic of the hypoxia-signaling cascade". Cell. Mol. Life Sci. 65 (7–8): 1133–49. doi:10.1007/s00018-008-7472-0. PMID 18202826. 
  27. ^ Weber LW, Boll M, Stampfl A (November 2004). "Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins". World J. Gastroenterol. 10 (21): 3081–7. PMID 15457548. 
  28. ^ Wheaton K, Atadja P, Riabowol K (1996). "Regulation of transcription factor activity during cellular aging". Biochem. Cell Biol. 74 (4): 523–34. doi:10.1139/o96-056. PMID 8960358. 
  29. ^ Meyyappan M, Atadja PW, Riabowol KT (1996). "Regulation of gene expression and transcription factor binding activity during cellular aging". Biol. Signals 5 (3): 130–8. doi:10.1159/000109183. PMID 8864058. 
  30. ^ Evan G, Harrington E, Fanidi A, Land H, Amati B, Bennett M (August 1994). "Integrated control of cell proliferation and cell death by the c-myc oncogene". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 345 (1313): 269–75. doi:10.1098/rstb.1994.0105. PMID 7846125. 
  31. ^ Boch J, Bonas U (2010). "XanthomonasAvrBs3 Family-Type III Effectors: Discovery and Function". Annual Review of Phytopathology 48: 419–436. doi:10.1146/annurev-phyto-080508-081936. PMID 19400638. 
  32. ^ Moscou MJ, Bogdanove AJ (December 2009). "A simple cipher governs DNA recognition by TAL effectors". Science 326 (5959): 1501. Bibcode:2009Sci...326.1501M. doi:10.1126/science.1178817. PMID 19933106. 
  33. ^ Boch J, Scholze H, Schornack S et al. (December 2009). "Breaking the code of DNA binding specificity of TAL-type III effectors". Science 326 (5959): 1509–12. Bibcode:2009Sci...326.1509B. doi:10.1126/science.1178811. PMID 19933107. 
  34. ^ Voytas DF, Joung JK (December 2009). "Plant science. DNA binding made easy". Science 326 (5959): 1491–2. Bibcode:2009Sci...326.1491V. doi:10.1126/science.1183604. PMID 20007890. 
  35. ^ a b Whiteside ST, Goodbourn S (April 1993). "Signal transduction and nuclear targeting: regulation of transcription factor activity by subcellular localisation". Journal of Cell Science 104 (4): 949–55. PMID 8314906. 
  36. ^ Bohmann D (November 1990). "Transcription factor phosphorylation: a link between signal transduction and the regulation of gene expression". Cancer cells (Cold Spring Harbor, N.Y. : 1989) 2 (11): 337–44. PMID 2149275. 
  37. ^ Weigel NL, Moore NL (2007). "Steroid Receptor Phosphorylation: A Key Modulator of Multiple Receptor Functions". Molecular Endocrinology 21 (10): 2311–9. doi:10.1210/me.2007-0101. PMID 17536004. 
  38. ^ Teif V.B., Rippe K. (2009). "Predicting nucleosome positions on the DNA: combining intrinsic sequence preferences and remodeler activities". Nucleic Acids Research 37 (17): 5641–55. doi:10.1093/nar/gkp610. PMC 2761276. PMID 19625488. 
  39. ^ Teif V.B., Rippe K.; Rippe (2010). "Statistical-mechanical lattice models for protein-DNA binding in chromatin". Journal of Physics: Condensed Matter 22 (41): 4105. arXiv:1004.5514. Bibcode:2010JPCM...22O4105T. doi:10.1088/0953-8984/22/41/414105. PMID 21386588. 
  40. ^ Sex steroid receptors in skeletal differentiation and epithelial neoplasia: is tissue-specific intervention possible? Copland JA, Sheffield-Moore M, Koldzic-Zivanovic N, Gentry S, Lamprou G, Tzortzatou-Stathopoulou F, Zoumpourlis V, Urban RJ, Vlahopoulos SA. Bioessays. 2009 Jun;31(6):629-41. doi: 10.1002/bies.200800138. Review. PMID: 19382224
  41. ^ Wärnmark A, Treuter E, Wright AP, Gustafsson J-Å (2003). "Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation". Mol. Endocrinol. 17 (10): 1901–9. doi:10.1210/me.2002-0384. PMID 12893880. 
  42. ^ Ma J, Ptashne M (October 1987). "A new class of yeast transcriptional activators". Cell 51 (1): 113–9. doi:10.1016/0092-8674(87)90015-8. PMID 3115591.  Sadowski I, Ma J, Triezenberg S, Ptashne M (October 1988). "GAL4-VP16 is an unusually potent transcriptional activator". Nature 335 (6190): 563–4. Bibcode:1988Natur.335..563S. doi:10.1038/335563a0. PMID 3047590.  Sullivan SM, Horn PJ, Olson VA, Koop AH, Niu W, Ebright RH, Triezenberg SJ (October 1998). "Mutational analysis of a transcriptional activation region of the VP16 protein of herpes simplex virus". Nucleic Acids Res. 26 (19): 4487–96. doi:10.1093/nar/26.19.4487. PMC 147869. PMID 9742254. Gill G, Ptashne M (October 1987). "Mutants of GAL4 protein altered in an activation function". Cell 51 (1): 121–6. doi:10.1016/0092-8674(87)90016-X. PMID 3115592.  Hope IA, Mahadevan S, Struhl K (June 1988). "Structural and functional characterization of the short acidic transcriptional activation region of yeast GCN4 protein". Nature 333 (6174): 635–40. Bibcode:1988Natur.333..635H. doi:10.1038/333635a0. PMID 3287180.  Hope IA, Struhl K (September 1986). "Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast". Cell 46 (6): 885–94. doi:10.1016/0092-8674(86)90070-X. PMID 3530496.  Drysdale CM, Dueñas E, Jackson BM, Reusser U, Braus GH, Hinnebusch AG (March 1995). "The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids". Mol. Cell. Biol. 15 (3): 1220–33. PMC 230345. PMID 7862116.  Regier JL, Shen F, Triezenberg SJ (February 1993). "Pattern of aromatic and hydrophobic amino acids critical for one of two subdomains of the VP16 transcriptional activator". Proc. Natl. Acad. Sci. U.S.A. 90 (3): 883–7. Bibcode:1993PNAS...90..883R. doi:10.1073/pnas.90.3.883. PMC 45774. PMID 8381535. 
  43. ^ a b Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (June 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics 89 (6): 756–68. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953. 
  44. ^ Uesugi M, Verdine GL (December 1999). "The alpha-helical FXXΦΦ motif in p53: TAF interaction and discrimination by MDM2". Proc. Natl. Acad. Sci. U.S.A. 96 (26): 14801–6. Bibcode:1999PNAS...9614801U. doi:10.1073/pnas.96.26.14801. PMC 24728. PMID 10611293. ; Uesugi M, Nyanguile O, Lu H, Levine AJ, Verdine GL (August 1997). "Induced alpha helix in the VP16 activation domain upon binding to a human TAF". Science 277 (5330): 1310–3. doi:10.1126/science.277.5330.1310. PMID 9271577. ; Choi Y, Asada S, Uesugi M (May 2000). "Divergent hTAFII31-binding motifs hidden in activation domains". J. Biol. Chem. 275 (21): 15912–6. doi:10.1074/jbc.275.21.15912. PMID 10821850. ; Lee CW, Arai M, Martinez-Yamout MA, Dyson HJ, Wright PE (March 2009). "Mapping the interactions of the p53 transactivation domain with the KIX domain of CBP". Biochemistry 48 (10): 2115–24. doi:10.1021/bi802055v. PMC 2765525. PMID 19220000. ; Goto NK, Zor T, Martinez-Yamout M, Dyson HJ, Wright PE (November 2002). "Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain". J. Biol. Chem. 277 (45): 43168–74. doi:10.1074/jbc.M207660200. PMID 12205094. ; Radhakrishnan I, Pérez-Alvarado GC, Parker D, Dyson HJ, Montminy MR, Wright PE (December 1997). "Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions". Cell 91 (6): 741–52. doi:10.1016/S0092-8674(00)80463-8. PMID 9413984. ; Zor T, Mayr BM, Dyson HJ, Montminy MR, Wright PE (November 2002). "Roles of phosphorylation and helix propensity in the binding of the KIX domain of CREB-binding protein by constitutive (c-Myb) and inducible (CREB) activators". J. Biol. Chem. 277 (44): 42241–8. doi:10.1074/jbc.M207361200. PMID 12196545. ; Brüschweiler S, Schanda P, Kloiber K, Brutscher B, Kontaxis G, Konrat R, Tollinger M (March 2009). "Direct observation of the dynamic process underlying allosteric signal transmission". J. Am. Chem. Soc. 131 (8): 3063–8. doi:10.1021/ja809947w. PMID 19203263. ; Liu GH, Qu J, Shen X (May 2008). "NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK". Biochim. Biophys. Acta 1783 (5): 713–27. doi:10.1016/j.bbamcr.2008.01.002. PMID 18241676. ; Bayly R, Murase T, Hyndman BD, Savage R, Nurmohamed S, Munro K, Casselman R, Smith SP, LeBrun DP (September 2006). "Critical role for a single leucine residue in leukemia induction by E2A-PBX1". Mol. Cell. Biol. 26 (17): 6442–52. doi:10.1128/MCB.02025-05. PMC 1592826. PMID 16914730. ; García-Rodríguez C, Rao A (June 1998). "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". J. Exp. Med. 187 (12): 2031–6. doi:10.1084/jem.187.12.2031. PMC 2212364. PMID 9625762. ; Mink S, Haenig B, Klempnauer KH (November 1997). "Interaction and functional collaboration of p300 and C/EBPbeta". Mol. Cell. Biol. 17 (11): 6609–17. PMC 232514. PMID 9343424. ; Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (June 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics 89 (6): 756–68. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953. 
  45. ^ Teufel DP, Freund SM, Bycroft M, Fersht AR (April 2007). "Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53". Proc. Natl. Acad. Sci. U.S.A. 104 (17): 7009–14. Bibcode:2007PNAS..104.7009T. doi:10.1073/pnas.0702010104. PMC 1855428. PMID 17438265. Teufel DP, Bycroft M, Fersht AR (May 2009). "Regulation by phosphorylation of the relative affinities of the N-terminal transactivation domains of p53 for p300 domains and Mdm2". Oncogene 28 (20): 2112–8. doi:10.1038/onc.2009.71. PMC 2685776. PMID 19363523. Feng H, Jenkins LM, Durell SR, Hayashi R, Mazur SJ, Cherry S, Tropea JE, Miller M, Wlodawer A, Appella E, Bai Y (February 2009). "Structural Basis for p300 Taz2/p53 TAD1 Binding and Modulation by Phosphorylation". Structure 17 (2): 202–10. doi:10.1016/j.str.2008.12.009. PMC 2705179. PMID 19217391. Ferreon JC, Lee CW, Arai M, Martinez-Yamout MA, Dyson HJ, Wright PE (April 2009). "Cooperative regulation of p53 by modulation of ternary complex formation with CBP/p300 and HDM2". Proc. Natl. Acad. Sci. U.S.A. 106 (16): 6591–6. Bibcode:2009PNAS..106.6591F. doi:10.1073/pnas.0811023106. PMC 2672497. PMID 19357310. Gamper AM, Roeder RG (April 2008). "Multivalent Binding of p53 to the STAGA Complex Mediates Coactivator Recruitment after UV Damage". Mol. Cell. Biol. 28 (8): 2517–27. doi:10.1128/MCB.01461-07. PMC 2293101. PMID 18250150. 
  46. ^ Fukasawa T, Fukuma M, Yano K, Sakurai H (February 2001). "A genome-wide analysis of transcriptional effect of Gal11 in Saccharomyces cerevisiae: an application of "mini-array hybridization technique"". DNA Res. 8 (1): 23–31. doi:10.1093/dnares/8.1.23. PMID 11258797. 
  47. ^ Badi L, Barberis A (August 2001). "Proteins that genetically interact with the Saccharomyces cerevisiae transcription factor Gal11p emphasize its role in the initiation-elongation transition". Mol. Genet. Genomics 265 (6): 1076–86. doi:10.1007/s004380100505. PMID 11523780. 
  48. ^ Kim YJ, Björklund S, Li Y, Sayre MH, Kornberg RD (May 1994). "A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II". Cell 77 (4): 599–608. doi:10.1016/0092-8674(94)90221-6. PMID 8187178. 
  49. ^ Suzuki Y, Nogi Y, Abe A, Fukasawa T (November 1988). "GAL11 protein, an auxiliary transcription activator for genes encoding galactose-metabolizing enzymes in Saccharomyces cerevisiae". Mol. Cell. Biol. 8 (11): 4991–9. PMC 365593. PMID 3062377. 
  50. ^ Fassler JS, Winston F (December 1989). "The Saccharomyces cerevisiae SPT13/GAL11 gene has both positive and negative regulatory roles in transcription". Mol. Cell. Biol. 9 (12): 5602–9. PMC 363730. PMID 2685570. 
  51. ^ Park JM, Kim HS, Han SJ, Hwang MS, Lee YC, Kim YJ (December 2000). "In vivo requirement of activator-specific binding targets of mediator". Mol. Cell. Biol. 20 (23): 8709–19. PMC 86488. PMID 11073972. 
  52. ^ Lu Z, Ansari AZ, Lu X, Ogirala A, Ptashne M (June 2002). "A target essential for the activity of a nonacidic yeast transcriptional activator". Proc. Natl. Acad. Sci. U.S.A. 99 (13): 8591–6. doi:10.1073/pnas.092263499. PMC 124323. PMID 12084920. 
  53. ^ Swanson MJ, Qiu H, Sumibcay L, Krueger A, Kim SJ, Natarajan K, Yoon S, Hinnebusch AG (April 2003). "A multiplicity of coactivators is required by Gcn4p at individual promoters in vivo". Mol. Cell. Biol. 23 (8): 2800–20. doi:10.1128/MCB.23.8.2800-2820.2003. PMC 152555. PMID 12665580. 
  54. ^ Bryant GO, Ptashne M (May 2003). "Independent recruitment in vivo by Gal4 of two complexes required for transcription". Mol. Cell 11 (5): 1301–9. doi:10.1016/S1097-2765(03)00144-8. PMID 12769853. 
  55. ^ Fishburn J, Mohibullah N, Hahn S (April 2005). "Function of a eukaryotic transcription activator during the transcription cycle". Mol. Cell 18 (3): 369–78. doi:10.1016/j.molcel.2005.03.029. PMID 15866178. 
  56. ^ Lim MK, Tang V, Le Saux A, Schüller J, Bongards C, Lehming N (November 2007). "Gal11p dosage-compensates transcriptional activator deletions via Taf14p". J. Mol. Biol. 374 (1): 9–23. doi:10.1016/j.jmb.2007.09.013. PMID 17919657. 
  57. ^ Lallet S, Garreau H, Garmendia-Torres C, Szestakowska D, Boy-Marcotte E, Quevillon-Chéruel S, Jacquet M (October 2006). "Role of Gal11, a component of the RNA polymerase II mediator in stress-induced hyperphosphorylation of Msn2 in Saccharomyces cerevisiae". Mol. Microbiol. 62 (2): 438–52. doi:10.1111/j.1365-2958.2006.05363.x. PMID 17020582. 
  58. ^ Dietz M, Heyken WT, Hoppen J, Geburtig S, Schüller HJ (May 2003). "TFIIB and subunits of the SAGA complex are involved in transcriptional activation of phospholipid biosynthetic genes by the regulatory protein Ino2 in the yeast Saccharomyces cerevisiae". Mol. Microbiol. 48 (4): 1119–30. doi:10.1046/j.1365-2958.2003.03501.x. PMID 12753200. 
  59. ^ Mizuno T, Harashima S (April 2003). "Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast". Mol. Genet. Genomics 269 (1): 68–77. doi:10.1007/s00438-003-0810-x. PMID 12715155. 
  60. ^ Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Näär AM (April 2008). "A nuclear receptor-like pathway regulating multidrug resistance in fungi". Nature 452 (7187): 604–9. doi:10.1038/nature06836. PMID 18385733. 
  61. ^ Thakur JK, Arthanari H, Yang F, Chau KH, Wagner G, Näär AM (February 2009). "Mediator subunit Gal11p/MED15 is required for fatty acid-dependent gene activation by yeast transcription factor Oaf1p". J. Biol. Chem. 284 (7): 4422–8. doi:10.1074/jbc.M808263200. PMID 19056732. 
  62. ^ Klein J, Nolden M, Sanders SL, Kirchner J, Weil PA, Melcher K (February 2003). "Use of a genetically introduced cross-linker to identify interaction sites of acidic activators within native transcription factor IID and SAGA". J. Biol. Chem. 278 (9): 6779–86. doi:10.1074/jbc.M212514200. PMID 12501245. 
  63. ^ Drysdale CM, Dueñas E, Jackson BM, Reusser U, Braus GH, Hinnebusch AG (March 1995). "The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids". Mol. Cell. Biol. 15 (3): 1220–33. PMC 230345. PMID 7862116. 
  64. ^ Milgrom E, West RW, Gao C, Shen WC (November 2005). "TFIID and Spt-Ada-Gcn5-acetyltransferase functions probed by genome-wide synthetic genetic array analysis using a Saccharomyces cerevisiae taf9-ts allele". Genetics 171 (3): 959–73. doi:10.1534/genetics.105.046557. PMC 1456853. PMID 16118188. 
  65. ^ Littlewood TD, Evan GI (1995). "Transcription factors 2: helix-loop-helix". Protein profile 2 (6): 621–702. PMID 7553065. 
  66. ^ Vinson C, Myakishev M, Acharya A, Mir AA, Moll JR, Bonovich M (September 2002). "Classification of Human B-ZIP Proteins Based on Dimerization Properties". Molecular and Cellular Biology 22 (18): 6321–35. doi:10.1128/MCB.22.18.6321-6335.2002. PMC 135624. PMID 12192032. 
  67. ^ Wintjens R, Rooman M (September 1996). "Structural classification of HTH DNA-binding domains and protein-DNA interaction modes". Journal of Molecular Biology 262 (2): 294–313. doi:10.1006/jmbi.1996.0514. PMID 8831795. 
  68. ^ Gehring WJ, Affolter M, Bürglin T (1994). "Homeodomain proteins". Annual review of biochemistry 63: 487–526. doi:10.1146/annurev.bi.63.070194.002415. PMID 7979246. 
  69. ^ Dahl E, Koseki H, Balling R (September 1997). "Pax genes and organogenesis". BioEssays : news and reviews in molecular, cellular and developmental biology 19 (9): 755–65. doi:10.1002/bies.950190905. PMID 9297966. 
  70. ^ Laity JH, Lee BM, Wright PE (February 2001). "Zinc finger proteins: new insights into structural and functional diversity". Current opinion in structural biology 11 (1): 39–46. doi:10.1016/S0959-440X(00)00167-6. PMID 11179890. 
  71. ^ Wolfe SA, Nekludova L, Pabo CO (2000). "DNA recognition by Cys2His2 zinc finger proteins". Annual review of biophysics and biomolecular structure 29: 183–212. doi:10.1146/annurev.biophys.29.1.183. PMID 10940247. 
  72. ^ Wang JC (March 2005). "Finding primary targets of transcriptional regulators". Cell Cycle 4 (3): 356–8. doi:10.4161/cc.4.3.1521. PMID 15711128. 
  73. ^ Semenza, Gregg L. (1999). Transcription factors and human disease. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-511239-3. 
  74. ^ Libermann TA, Zerbini LF (February 2006). "Targeting transcription factors for cancer gene therapy". Curr Gene Ther 6 (1): 17–33. doi:10.2174/156652306775515501. PMID 16475943. 
  75. ^ Moretti P, Zoghbi HY (June 2006). "MeCP2 dysfunction in Rett syndrome and related disorders". Curr. Opin. Genet. Dev. 16 (3): 276–81. doi:10.1016/j.gde.2006.04.009. PMID 16647848. 
  76. ^ Chadwick LH, Wade PA (April 2007). "MeCP2 in Rett syndrome: transcriptional repressor or chromatin architectural protein?". Curr. Opin. Genet. Dev. 17 (2): 121–5. doi:10.1016/j.gde.2007.02.003. PMID 17317146. 
  77. ^ Maestro MA, Cardalda C, Boj SF, Luco RF, Servitja JM, Ferrer J (2007). "Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth". Endocr Dev 12: 33–45. doi:10.1159/0000109603 (inactive 10 January 2009). PMID 17923767. 
  78. ^ Al-Quobaili F, Montenarh M (April 2008). "Pancreatic duodenal homeobox factor-1 and diabetes mellitus type 2 (review)". Int. J. Mol. Med. 21 (4): 399–404. doi:10.3892/ijmm.21.4.399. PMID 18360684. 
  79. ^ Lennon PA, Cooper ML, Peiffer DA, Gunderson KL, Patel A, Peters S, Cheung SW, Bacino CA (April 2007). "Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review". Am. J. Med. Genet. A 143A (8): 791–8. doi:10.1002/ajmg.a.31632. PMID 17330859. 
  80. ^ van der Vliet HJ, Nieuwenhuis EE (2007). "IPEX as a Result of Mutations in FOXP3". Clin. Dev. Immunol. 2007: 89017. doi:10.1155/2007/89017. PMC 2248278. PMID 18317533. 
  81. ^ Iwakuma T, Lozano G, Flores ER (July 2005). "Li-Fraumeni syndrome: a p53 family affair". Cell Cycle 4 (7): 865–7. doi:10.4161/cc.4.7.1800. PMID 15917654. 
  82. ^ http://ajp.amjpathol.org/cgi/content/full/165/5/1449 "Roles and Regulation of Stat Family Transcription Factors in Human Breast Cancer" 2004
  83. ^ http://www.ias.surrey.ac.uk/reports/hox-report.html "Transcription factors as targets and markers in cancer" Workshop 2007
  84. ^ Overington JP, Al-Lazikani B, Hopkins AL (2006). "How many drug targets are there?". Nature reviews. Drug discovery 5 (12): 993–6. doi:10.1038/nrd2199. PMID 17139284. 
  85. ^ Gronemeyer H, Gustafsson JA, Laudet V (November 2004). "Principles for modulation of the nuclear receptor superfamily". Nat Rev Drug Discov 3 (11): 950–64. doi:10.1038/nrd1551. PMID 15520817. 
  86. ^ Bustin SA, McKay IA (June 1994). "Transcription factors: targets for new designer drugs". Br. J. Biomed. Sci. 51 (2): 147–57. PMID 8049612. 
  87. ^ Butt TR, Karathanasis SK (1995). "Transcription factors as drug targets: opportunities for therapeutic selectivity". Gene Expr. 4 (6): 319–36. PMID 7549464. 
  88. ^ Papavassiliou AG (August 1998). "Transcription-factor-modulating agents: precision and selectivity in drug design". Mol Med Today 4 (8): 358–66. doi:10.1016/S1357-4310(98)01303-3. PMID 9755455. 
  89. ^ Ghosh D, Papavassiliou AG (2005). "Transcription factor therapeutics: long-shot or lodestone". Curr. Med. Chem. 12 (6): 691–701. doi:10.2174/0929867053202197. PMID 15790306. 
  90. ^ Moellering RE, Cornejo M, Davis TN, Del Bianco C, Aster JC, Blacklow SC, Kung AL, Gilliland DG, Verdine GL, Bradner JE (November 2009). "Direct inhibition of the NOTCH transcription factor complex". Nature 462 (7270): 182–8. Bibcode:2009Natur.462..182M. doi:10.1038/nature08543. PMC 2951323. PMID 19907488. Lay summaryThe Scientist. 
  91. ^ F. Parcy et al., (2014). "A promiscuous intermediate underlies the evolution of LEAFY DNA binding specificity." Science 343 (6171) : 645-648. doi: 10.1126/science.1248229
  92. ^ EntrezGene database
  93. ^ Grau J., Ben-Gal I., Posch S., Grosse I. (2006). "VOMBAT: Prediction of Transcription Factor Binding Sites using Variable Order Bayesian Trees,". Nucleic Acids Research, vol. 34, issue W529–W533. 
  94. ^ http://www.eng.tau.ac.il/~bengal/VOMBAT.pdf
  95. ^ Wenta N, Strauss H, Meyer S, Vinkemeier U (2008). "Tyrosine phosphorylation regulates the partitioning of STAT1 between different dimer conformations". Proc Natl Acad Sci U S A 105 (27): 9238–43. Bibcode:2008PNAS..105.9238W. doi:10.1073/pnas.0802130105. PMC 2453697. PMID 18591661. 
  96. ^ Sermeus A, Cosse JP, Crespin M, Mainfroid V, de Longueville F, Ninane N, Raes M, Remacle J, Michiels C (2008). "Hypoxia induces protection against etoposide-induced apoptosis: molecular profiling of changes in gene expression and transcription factor activity". Mol Cancer 7: 27. doi:10.1186/1476-4598-7-27. PMC 2330149. PMID 18366759. 
  97. ^ Orphanides G, Lagrange T, Reinberg D (1996). "The general transcription factors of RNA polymerase II". Genes Dev. 10 (21): 2657–83. doi:10.1101/gad.10.21.2657. PMID 8946909. 
  98. ^ a b Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 125–126. ISBN 1-4160-2328-3. 
  99. ^ Stegmaier P, Kel AE, Wingender E (2004). "Systematic DNA-binding domain classification of transcription factors". Genome informatics. International Conference on Genome Informatics 15 (2): 276–86. PMID 15706513. 
  100. ^ Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Reuter I, Chekmenev D, Krull M, Hornischer K, Voss N, Stegmaier P, Lewicki-Potapov B, Saxel H, Kel AE, Wingender E (2006). "TRANSFAC® and its module TRANSCompel®: transcriptional gene regulation in eukaryotes". Nucleic Acids Res. 34 (Database issue): D108–10. doi:10.1093/nar/gkj143. PMC 1347505. PMID 16381825. 
  101. ^ "TRANSFAC database". Retrieved 5 August 2007. 

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