Alternative titles; symbols
HGNC Approved Gene Symbol: TAF3
Cytogenetic location: 10p14 Genomic coordinates (GRCh38) : 10:7,818,505-8,016,631 (from NCBI)
The highly conserved RNA polymerase II (pol II) transcription factor TFIID (see TAF1; 313650) comprises the TATA box-binding protein (TBP; 600075) and a set of TBP-associated factors (TAFs), including TAF3. TAFs contribute to promoter recognition and selectivity and act as antiapoptotic factors (Gangloff et al., 2001). In addition to its role in TFIID, TAF3 can interact with several other transcription factors to control gene expression (Liu et al., 2011).
By EST database searching for sequences similar to the histone fold domain (HFD) of yeast Tafii47, followed by probing a HeLa cell cDNA library, Gangloff et al. (2001) obtained a partial cDNA encoding TAF3, which they termed TAFII140. The deduced 727-amino acid protein contains an N-terminal HFD and is highly homologous to mouse Tafii140. The 932-amino acid mouse protein has a C-terminal plant homeodomain (PHD) finger, and genomic database analysis suggested that this motif is present in human TAF3.
Using Western blot analysis, Liu et al. (2011) found that Taf3 was highly expressed in mouse embryonic stem cell lines and hybridomas, with much lower expression in other cell types. Low Taf3 expression was detected in mouse spleen, but not in heart, brain, lung, or liver. Taf3 was downregulated following differentiation of embryonic stem cells into embryoid bodies.
Using yeast 2-hybrid analysis, Gangloff et al. (2001) showed that mouse Tafii140 interacted with human TAFII30 (TAF10; 600475) through their HFDs. Immunoprecipitation analysis detected nuclear expression of TAF3 as a 140-kD protein that apparently formed complexes with TBP and TAFII18 (TAF13; 600774), as well as with SAP130 (SF3B3; 605592) and GCN5 (see 602301).
Trimethylation of histone H3 (see 602810) at lys4 (H3K4me3) is a hallmark of active human promoters. Using stable isotope labeling by amino acids in cell culture (SILAC)-based proteomic screening, Vermeulen et al. (2007) showed that TFIID bound directly to H3K4me3 via the PHD of the TFIID subunit TAF3. Selective loss of H3K4me3 reduced transcription from and TFIID binding to a subset of promoters in vivo. Equilibrium binding assays and competition experiments indicated that the TAF3 PHD finger was highly selective for H3K4me3. In transient assays, TAF3 could act as a transcriptional activator in a PHD finger-dependent manner. Asymmetric dimethylation of H3 at arg2 selectively inhibited binding of TFIID to H3K4me3, whereas acetylation of H3 at lys9 and lys14 potentiated interaction of TFIID with H3K4me3. Vermeulen et al. (2007) concluded that there is crosstalk between histone modifications and TFIID.
By knockdown of Taf3 expression via short hairpin RNA, Liu et al. (2011) found that Taf3 had a critical role in maintaining pluripotency of mouse embryonic stem cells. Gene expression profiling revealed that knockdown of Taf3 predominantly resulted in expression of a neural program and downregulation of an endodermal program. Chromatin immunoprecipitation and sequencing revealed that binding of Taf3 at promoters positively correlated with the presence of pol II, Taf1, and Tbp. Using genomewide binding studies, Liu et al. (2011) identified 3 other classes of chromosomal regions enriched in Taf3 binding: those that included Oct4 (POU5F1; 164177), Nanog (607937), Sox2 (184429), and mediator components (see 604311); those that included Ctcf (604167) and the cohesin subunits Smc1a (300040) and Smc3 (606062); and those that were enriched for Taf3 alone. Association of Taf3 with Ctcf and cohesin at core promoters was associated with DNA looping from distal sites. DNA looping was specifically observed with the Taf3-activated genes Mapk3 (601795) and Psmd1 (617842). Expression of these genes was reduced following knockdown of either Taf3 or Ctcf and was further reduced with depletion of both Taf3 and Ctcf. Liu et al. (2011) concluded that TAF3 can bind DNA in several different contexts and that TAF3 has a major role in maintaining embryonic stem cell pluripotency.
Hartz (2012) mapped the TAF3 gene to chromosome 10p14 based on an alignment of the TAF3 sequence (GenBank AJ292190) with the genomic sequence (GRCh37).
Gangloff, Y.-G., Pointud, J.-C., Thuault, S., Carre, L., Romier, C., Muratoglu, S., Brand, M., Tora, L., Couderc, J.-L., Davidson, I. The TFIID components human TAF(II)140 and Drosophila BIP2 (TAF(II)155) are novel metazoan homologues of yeast TAF(II)47 containing a histone fold and a PHD finger. Molec. Cell. Biol. 21: 5109-5121, 2001. [PubMed: 11438666] [Full Text: https://doi.org/10.1128/MCB.21.15.5109-5121.2001]
Hartz, P. A. Personal Communication. Baltimore, Md. 9/21/2012.
Liu, Z., Scannell, D. R., Eisen, M. B., Tjian, R. Control of embryonic stell cell lineage commitment by core promoter factor, TAF3. Cell 146: 720-731, 2011. [PubMed: 21884934] [Full Text: https://doi.org/10.1016/j.cell.2011.08.005]
Vermeulen, M., Mulder, K. W., Denissov, S., Pim Pijnappel, W. W. M., van Schaik, F. M. A., Varier, R. A., Baltissen, M. P. A., Stunnenberg, H. G., Mann, M., Timmers, H. T. M. Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131: 58-69, 2007. [PubMed: 17884155] [Full Text: https://doi.org/10.1016/j.cell.2007.08.016]