General transcription factor

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Transcription factors. In the middle part above the promoter, the pink color part of the transcription factors are the General Transcription Factors.

General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites (promoter) on DNA to activate transcription of genetic information from DNA to messenger RNA. GTFs, RNA polymerase, and the mediator multiple protein complex constitute the basic transcriptional apparatus that bind to the promoter, then start transcription.[1] GTFs are also intimately involved in the process of gene regulation, and most are required for life.[2]

Transcription factors is a protein that binds to specific DNA sequences (enhancer or promoter), alone or with other proteins in a complex to control the rate of transcription of genetic information from DNA to messenger RNA, by promoting as an activator, or blocking as a repressor the recruitment of RNA polymerase.[3][4][5][6][7] As a class of protein transcription factors, General transcription factors bind to promoter on DNA sequence along or form a large transcription preinitiation complex to only activate transcription. General transcription factors are necessary for transcription to occur.[8][9][10]

Types[edit]

In bacteria, transcription initiation requires an RNA polymerase and a single GTF: sigma factor.

Transcription preinitiation complex

In archaea and eukaryotes, transcription initiation requires an RNA polymerase and a set of multiple GTFs form a transcription preinitiation complex. The Transcription initiation by eukaryotic RNA polymerase II involves the following GTFs:[11][12]

Function and Mechanism[edit]

In bacteria-Sigma factor (σ factor)[edit]

A sigma factor is a protein needed only for initiation of RNA synthesis in bacteria.[13] Sigma factors provide promoter recognition specificity to the RNA polymerase (RNAP) and contribute to DNA strand separation; they then dissociate from RNA polymerase core enzyme following transcription initiation.[14] The mechanism is RNA polymerase core associates with the sigma factor to form RNA polymerase holoenzyme. Sigma factor reduces the affinity of RNA polymerase for nonspecific DNA while increasing specificity for promoters, allowing transcription to initiate at correct sites. The core enzyme of RNA polymerase has five subunits (protein subunits) (~400 kDa).[15] Because of the RNA polymerase association with sigma factor, the complete RNA polymerase therefore has 6 subunits: the sigma subunit-in addition to the two alpha (α), one beta (β), one beta prime (β'), and one omega (ω) subunits that make up the core enzyme(~450 kDa). In addition, many bacteria can have multiple alternative σ factors. The level and activity of the alternative σ factors are highly regulated and can vary depending on environmental or developmental signals. [16]

In archaea and eukaryotes (Transcription preinitiation complex)[edit]

The transcription preinitiation complex is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. It attaches to the promoter of the DNA (e.g., TATA box) and helps position the RNA polymerase II to the gene transcription start sites, denatures the DNA, and then starts transcription.[17][18][19][20]

Transcription preinitiation complex assembly[edit]

The assembly of transcription preinitiation complex follows these steps:

  1. TATA binding protein (TBP), a subunit of TFIID (the largest GTF) binds to the promoter (TATA box), creating a sharp bend in the promoter DNA. Then the TBP-TFIIA interactions recruit TFIIA to the promoter.
  2. TBP-TFIIB interactions recruit TFIIB to the promoter. RNA polymerase II and TFIIF are assembling to form Polymerase II complex. TFIIB help the Pol II complex bind correctly.
  3. TFIIE and TFIIH then bind to the complex, form the transcription preinitiation complex. TFIIA/B/E/H leave once RNA elongation begins. TFIID will stay until elongation is finish.
  4. Subunits within TFIIH that have ATPase and helicase activity create negative superhelical tension in the DNA. This negative superhelical tension causes approximately one turn of DNA to unwind and form the transcription bubble.
  5. The template strand of the transcription bubble engages with the RNA polymerase II active site. Then RNA synthesis starts.

Research Examples about GTFs[edit]

Interaction of the Human Androgen Receptor Transactivation Function with the General Transcription Factor TFIIF[21][edit]

This experiment trying to understand how the human androgen receptor regulate the gene transcription through the interaction with GTF. The human androgen receptor (AR) is a ligand-activated transcription factor that regulates genes important for male sexual differentiation and development. In this experiment, a panel of general transcription factors was screened for interactions with the receptor transactivation domain. A polypeptide containing amino acids 142–485 of the human receptor was expressed and purified. They use this region is because in the previous study, they have already known that this region plays important role in the full activity of human AR. Then the purified protein was allowed to adsorb onto the surface of a microtiter plate and incubated with 35S-labeled General transcription factors TFIIB, TBP, TFIIE, TFIIF, and TFIIH. The result showed that this region of the Human Androgen Receptor N terminus containing the transactivation function bound selectively to the basal transcription factors TBP and TFIIF. This means that TBP and TFIIF play the most important role in the regulation of male sexual differentiation and development through their interaction with Human AR and its ligand. Please see external link for the original full text and figures.

Acetylation of General Transcription Factors by Histone Acetyltransferases[22][edit]

The acetylation of histones can increase the accessibility of nucleosomal DNA to transcription factors. The characters of these three histones acetyltransferases: Human GCN5 homolog PCAF (p300/CBP-associated factor), the transcription coactivator p300/CBP, and TAFII250 have provided a potential explanation for the relationship between histone acetylation and transcriptional activation. Therefore, in this experiment, they were trying to know if the acetyltransferases could acetylate directly to GTF to affect transcription.The recombinant transcription factors studied were TFIIA (p55 and p12 subunits), TFIIB, TATA-binding protein (TBP), the α and β subunits of TFIIE, TFIIF (RAP30 and RAP74 subunits), and the core histones H3 and H4. They first normalized the amount of each factor studied by Coomassie blue staining after SDS-polyacrylamide gel electrophoresis. Then they incubated each transcription factor with recombinant PCAF, p300 or TAFII250 in the presence of [3H]acetyl CoA. The result showed that the β subunit of TFIIE was acetylated by all three enzymes. Both subunits of TFIIF-RAP74 and RAP30 were acetylated by PCAF and p300, but TAFII250 had little effect on this factor. Therefore, the acetyltransferases can acetylate directly to GTF to affect transcription. Please see external link for the original full text and figures.

References[edit]

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  4. ^ Karin M (1990). "Too many transcription factors: positive and negative interactions". New Biol. 2 (2): 126–31. PMID 2128034.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ Lee TI, Young RA (2000). "Transcription of eukaryotic protein-coding genes". Annu. Rev. Genet. 34 (1): 77–137. doi:10.1146/annurev.genet.34.1.77. PMID 11092823. 
  12. ^ 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. 
  13. ^ Gruber, Tanja M; Gross, Carol A (Oct 1, 2003). "MULTIPLE SIGMA SUBUNITS AND THE PARTITIONING OF BACTERIAL TRANSCRIPTION SPACE". Annual Review of Microbiology. Annual Reviews. pp. 441–466. doi:10.1146/annurev.micro.57.030502.090913. PMID 14527287. 
  14. ^ Borukhov, Sergei; Nudler, Evgeny (April 2003). RNA polymerase holoenzyme: structure, function and biological implications 6. Current Opinion in Microbiology. pp. 93–100. ISSN 1369-5274. 
  15. ^ Ebright RH (2000). "RNA polymerase: structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II". J Mol Biol 304 (5): 687–98. doi:10.1006/jmbi.2000.4309. PMID 11124018.
  16. ^ Chandrangsu, Pete, and Helmann, John D(Mar 2014) Sigma Factors in Gene Expression. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net. doi: 10.1002/9780470015902.a0000854.pub3
  17. ^ 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.
  18. ^ Kornberg RD (2007). "The molecular basis of eukaryotic transcription". Proc. Natl. Acad. Sci. U.S.A. 104 (32): 12955–61. doi:10.1073/pnas.0704138104.PMC 1941834. PMID 17670940.
  19. ^ Kim TK, Lagrange T, Wang YH, Griffith JD, Reinberg D, Ebright RH (1997). "Trajectory of DNA in the RNA polymerase II transcription preinitiation complex". Proc Natl Acad Sci USA 94 (23): 12268-73. doi:10.1073/pnas.94.23.12268. PMC 24903. PMID 9356438.
  20. ^ Kim TK, Ebright RH, Reinberg D (2000). "Mechanism of ATP-dependent promoter melting by transcription factor IIH". Science 288 (5470): 1418–22.doi:10.1126/science.288.5470.1418. PMID 10827951.
  21. ^ Iain, J. McEwan; Jan-Åke, Gustafsson (August 5, 1997). "Interaction of the human androgen receptor transactivation function with the general transcription factor TFIIF". The National Academy of Sciences of the USA 94. PMID 9238003. 
  22. ^ Axel, Imhof; Xiang-Jiao, Yang; Vasily, V Ogryzko; Yoshihiro, Nakatani; Alan, P Wolffe; Hui, Ge (September 1, 1997). "Acetylation of general transcription factors by histone acetyltransferases". Current Biology 7 (9): 689-692. doi:10.1016/S0960-9822(06)00296-X. 

External links[edit]