TAF7l
TATA-box binding protein associated factor 7-like also known as CT40 is a protein that in humans is encoded by the TAF7l gene.[5] It is a close homologue to the TAF7 gene, although its function may be different. Currently, little is known about this gene. It was originally demonstrated to be a testis-specific gene based on RT-PCR experiments on tissue extracts,[5] however, it has now been found in white and brown adipose tissue,[6] as well as in certain types of cancer.[7]
Function
Function in Adipose Tissue Formation
Studies conducted on knockout animals have revealed that Taf7l makes important contributions in determining the fate of mesenchymal stem cells. Importantly, Zhou et al.[6] found that in Taf7L−/− (Taf7L knockout)animals have decreased fat pads that are infiltrated by skeletal muscle tissue. Using RNA-seq and Gene Ontology Enrichment (GO), this same group found that there was an increase in GO terms (and thus gene categories) that werew involved in skeletal and muscle development. Combined with in vitro evidence, it appears that Taf7l is capable of initiating brown fat (the so-called healthy fat) production. Additionally, they found that together with PPARgamma, Taf7l likely can regulate the binding of the TFIID/RNA Polymerase II (RNAP II) complex. Specifically, the presence of Taf7l may alter chromatin looping and thus the association of distal enhancer sequences to BAT specific gene promoters, like Cidea and Scd1.
Function in Cancer
Recently, frameshift mutation was found to be present in 3 patients with colorectal cancer.[7] Specifically, a poly-A mono-nucleotide repeat region in Exon 6 of Taf7l was found to be missing one nucleotide (deletion mutation), resulting in a frameshift mutation. It has additionally been found to be decreased in 58% of Acute Myelogenous Leukemai (AML).
Function in spermatogenesis: Reciprocity with TAF7
Much of the initial work came from Pointud et al.[5] They found that Taf7l has dual functionality during spermatogenesis. In early stage spermatocytes, for example in primary spermatocytes (still diploid at this point), TAF7l is located in the cytoplasm, while TATA-binding protein (TBP) complex is located in the nucleus. Then, TAF7l slowly transitions to the nucleus during the mid-stage pachytene cell, where there is also a dramatic increase in TBP protein expression in the nucleus as well. Additionally, there is a reciprocal relationship to that of TAF7 expression: Unlike TAF7l, TAF7 at early stages is expressed in the nucleus, and thus separated from TAF7l. Then, at later stages, when TAF7l transitions into the nucleus, which happens around the time when the somatic (diploid) to germ cell (haploid) transition occurs, TAF7 dramatically declines. This may indicate that TAF7l plays an important role in regulating the TFIID during development of the sperm. Pointud et al. (2003) speculate that TAF7l may "bookmark" certain genes for expression or repression in the haploid spermatocyte.
Function during Transcription
A definitive role for TAF7l during transcription still remains elusive. Yeast-2-hybrid screens have identified that TAF7l strongly interacts with TAF1 in exactly the same region (amino acids 1170-1226 of TAF1) that TAF7 binds to and inactivates TAF1's acetyltransferase (AT) function.[5] Thus, it is likely that TAF7l shares a similar role to TAF7, in inhibiting TAF1 and thus, the activity of the TFIID complex. TAF7l localizes in a different compartment relative to TBP during early spermatogenesis, implying a TBP-independent function that awaits further study. Additionally, Chromosome Conformation Capture, has identified a role of TAF7 in directly mediating binding of enhancer elements to promoter sequences that TFIID binds to.[6] This further suggests that TAF7l replaces the function of TAF7, as TAF7 has also been demonstrated to bind to and regulate gene (Vitamin D3 or Thyroid Hormone, for example) expression in a promoter specific fashion [5]
- G. S. Gupta (2 Jul 2006). Proteomics of Spermatogenesis. Springer Science & Business Media. p. 327. ISBN 9780387276557.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000102387 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000009596 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e Pointud JC, Mengus G, Brancorsini S, Monaco L, Parvinen M, Sassone-Corsi P, Davidson I (May 2003). "The intracellular localisation of TAF7L, a paralogue of transcription factor TFIID subunit TAF7, is developmentally regulated during male germ-cell differentiation". Journal of Cell Science. 1 (116): 1847–58. PMID 12665565.
- ^ a b c https://elifesciences.org/content/3/e02811
- ^ a b Oh HR, An CH, Yoo NJ, Lee SH (July 2015). "Frameshift mutations of TAF7L gene, a core component for transcription by RNA polymerase II, in colorectal cancers". Pathology of Oncology Research. 21 (3). doi:10.1007/s12253-014-9832-4. PMID 25098277.