Alternative titles; symbols
HGNC Approved Gene Symbol: TAF9
Cytogenetic location: 5q13.2 Genomic coordinates (GRCh38): 5:69,364,743-69,369,824 (from NCBI)
RNA polymerase II transcription factor IID (see 313650) is a complex of the TATA binding protein (600075) and a variety of TBP-associated factors (TAFs). The TAFs are required for activated rather than basal transcription and serve to mediate signals between various activators and the basal transcriptional machinery.
Klemm et al. (1995) cloned a human TFIID subunit, which they termed hTAFII32. The 32-kD protein was isolated from HeLa cell nuclear extracts and partially sequenced. A degenerate oligomer was designed and used to probe a human HeLa cell cDNA library. The identified cDNA has a deduced amino acid sequence of 264 residues and is related to the Drosophila TAFII40.
Lu and Levine (1995) also cloned TAF9, which they called TAFII31.
Santama et al. (2005) determined that human CINAP (AK6; 619357) and TAFIID32 are generated from the same locus as alternatively spliced transcripts that share exons 1 and 2. However, TAFIID32 uses an ATG start codon downstream of the CINAP ATG start codon in a different reading frame, resulting in 2 distinct proteins with no shared amino acid sequence, despite a common 5-prime region in the transcripts. Northern blot and semiquantitative RT-PCR revealed that both transcripts were expressed in all human tissues and cell lines tested. The unusual gene arrangement for human CINAP and TAFIID32 is conserved in mammals, including chimp, rat, mouse, and dog, but not in other vertebrates examined, including fish and amphibians, where the CINAP and TAFIID32 orthologs are encoded at separate loci.
Klemm et al. (1995) showed that TAFII32 interacts with GTF2B (189963) and with the viral transcriptional transactivator VP16. The authors showed that recombinantly expressed TAFII32 was functional in a partial recombinant TFIID complex and that the recombinant complex mediated activation by a GAL4-VP16 fusion protein.
Using immunoprecipitation and binding analyses, Lu and Levine (1995) showed that TAF9 interacts with the N-terminal domain of p53 (191170) at sites identical to those bound by MDM2 (164785), the major cellular negative regulator of p53 activity. Antibodies to TAF9 inhibited p53-activated transcription. Lu and Levine (1995) concluded that p53 activity is regulated by 2 proteins competing for the same region of the p53 protein.
Using a conditional TAF9 knockout cell line in chicken DT40 cells, Chen and Manley (2000) provided evidence that TAF9 was not generally required for RNA pol II-mediated transcription in vivo, although depletion of TAF9 resulted in codepletion of many other TAFs and apoptotic cell death. In additional studies with DT40-TAF9 cells, Chen and Manley (2003) demonstrated that depletion of TAF9 causes disruption of TFIID, illustrating the key role of TAF9 in TFIID structural integrity and the functional competence of TFIID with greatly reduced TAF content. Complementation analyses with various TAF9 chimeras revealed stringent sequence requirements of the TAF9 histone fold motifs. Human TAF9 and the related factor TAF9L (TAF9B; 300754) both restored essential functions of chicken TAF9 in DT40 cells.
Frontini et al. (2005) demonstrated that TAF9 and TAF9B are present in both TFIID and TFTC (TATA-binding protein-free TAF-containing complex) complexes and have both distinct and overlapping functions. TAF9 was ubiquitously expressed, together with TAF9B, in all cell types tested. In vivo and in vitro experiments showed similar interactions of TAF9 and TAF9B with TAF6 (602955) histone fold pairs. Stimulation of apoptosis in HeLa cells increased TAF9 and TAF9B expression levels about 6- to 9-fold and about 1.5-fold, respectively. TAF9B overexpression had a weaker effect on p53 stabilization than TAF9 in MCF7 and HeLa cells. SiRNA knockdown experiments showed that both genes are essential for cell viability. Gene expression analysis of cells treated with TAF9 or TAF9B siRNAs indicated that the 2 proteins regulate different sets of genes with only a small overlap.
Cryoelectron Microscopy
Bieniossek et al. (2013) presented the structure of the human core-TFIID complex, consisting of 2 copies each of TAF4 (601796), TAF5 (601787), TAF6, TAF9, and TAF12 (600773), determined by cryoelectron microscopy at 11.6-angstrom resolution. The structure revealed a 2-fold symmetric, interlaced architecture, with pronounced protrusions, that accommodates all conserved structural features of the TAFs including the histone folds. Bieniossek et al. (2013) further demonstrated that binding of 1 TAF8 (609514)-TAF10 (600475) complex breaks the original symmetry of the core-TFIID. Bieniossek et al. (2013) proposed that the resulting asymmetric structure serves as a functional scaffold to nucleate holo-TFIID assembly, by accreting 1 copy each of the remaining TAFs and TBP.
By analysis of human/rodent somatic cell hybrids, PCR amplification of monochromosomal hybrids, and FISH, Evans et al. (1999) mapped the TAF2G gene to chromosome 5q11.2-q13.1.
By genomic sequence analysis, Santama et al. (2005) mapped the TAF9 gene to chromosome 5q13.2. The TAF9 and AK6 genes overlap one another and share the same first 2 exons.
Bieniossek, C., Papai, G., Schaffitzel, C., Garzoni, F., Chaillet, M., Scheer, E., Papadopoulos, P., Tora, L., Schultz, P., Berger, I. The architecture of human general transcription factor TFIID core complex. Nature 493: 699-702, 2013. [PubMed: 23292512] [Full Text: https://doi.org/10.1038/nature11791]
Chen, Z., Manley, J. L. Robust mRNA transcription in chicken DT40 cells depleted of TAF(II)31 suggests both functional degeneracy and evolutionary divergence. Molec. Cell Biol. 20: 5064-5076, 2000. [PubMed: 10866663] [Full Text: https://doi.org/10.1128/MCB.20.14.5064-5076.2000]
Chen, Z., Manley, J. L. In vivo functional analysis of the histone 3-like TAF9 and a TAF9-related factor, TAF9L. J. Biol. Chem. 278: 35172-35183, 2003. [PubMed: 12837753] [Full Text: https://doi.org/10.1074/jbc.M304241200]
Evans, S. C., Foster, C. J., El-Naggar, A. K., Lozano, G. Mapping and mutational analysis of the human TAF2G gene encoding a p53 cofactor. Genomics 57: 182-183, 1999. [PubMed: 10191103] [Full Text: https://doi.org/10.1006/geno.1999.5745]
Frontini, M., Soutoglou, E., Argentini, M., Bole-Feysot, C., Jost, B., Scheer, E., Tora, L. TAF9b (formerly TAF9L) is a bona fide TAF that has unique and overlapping roles with TAF9. Molec. Cell. Biol. 25: 4638-4649, 2005. [PubMed: 15899866] [Full Text: https://doi.org/10.1128/MCB.25.11.4638-4649.2005]
Klemm, R. D., Goodrich, J. A., Zhou, S., Tjian, R. Molecular cloning and expression of the 32-kDa subunit of human TFIID reveals interactions with VP16 and TFIIB that mediate transcriptional activation. Proc. Nat. Acad. Sci. 92: 5788-5792, 1995. [PubMed: 7597030] [Full Text: https://doi.org/10.1073/pnas.92.13.5788]
Lu, H., Levine, A. J. Human TAFII31 protein is a transcriptional coactivator of the p53 protein. Proc. Nat. Acad. Sci. 92: 5154-5158, 1995. [PubMed: 7761466] [Full Text: https://doi.org/10.1073/pnas.92.11.5154]
Santama, N., Ogg, S. C., Malekkou, A., Zographos, S. E., Weis, K., Lamond, A. I. Characterization of hCINAP, a novel coilin-interacting protein encoded by a transcript from the transcription factor TAFIID32 locus. J. Biol. Chem. 280: 36429-36441, 2005. [PubMed: 16079131] [Full Text: https://doi.org/10.1074/jbc.M501982200]