TAF9b (Formerly TAF9L) Is a Bona Fide TAF That Has Unique and Overlapping Roles with TAF9

Abstract

TFIID plays a key role in transcription initiation of RNA polymerase II preinitiation complex assembly. TFIID is comprised of the TATA box binding protein (TBP) and 14 TBP-associated factors (TAFs). A second set of transcriptional regulatory multiprotein complexes containing TAFs has been described (called SAGA, TFTC, STAGA, and PCAF/GCN5). Using matrix-assisted laser desorption ionization mass spectrometry, we identified a novel TFTC subunit, human TAF9Like, encoded by a TAF9 paralogue gene. We show that TAF9Like is a subunit of TFIID, and thus, it will be called TAF9b. TFIID and TFTC complexes in which both TAF9 and TAF9b are present exist. In vitro and in vivo experiments indicate that the interactions between TAF9b and TAF6 or TAF9 and TAF6 histone fold pairs are similar. We observed a differential induction of TAF9 and TAF9b during apoptosis that, together with their different ability to stabilize p53, points to distinct requirements for the two proteins in gene regulation. Small interfering RNA (siRNA) knockdown of TAF9 and TAF9b revealed that both genes are essential for cell viability. Gene expression analysis of cells treated with either TAF9 or TAF9b siRNAs indicates that the two proteins regulate different sets of genes with only a small overlap. Taken together, these data demonstrate that TAF9 and TAF9b share some of their functions, but more importantly, they have distinct roles in the transcriptional regulatory process.Transcription initiation of protein-encoding genes by RNA polymerase II (Pol II) requires the transcription factor TFIID that is comprised of the TATA binding protein (TBP) and series of TBP-associated factors (TAFs) (1, 6, 57). In human HeLa cells, we showed that different human TFIID complexes containing or lacking TAF10 which exhibit functionally distinct properties exist (6,7,25). Cell type-specific TFIID complexes have been found to be composed of core TAFs and cell typespecific TAFs. TAF4b was found to be enriched in differentiated human B lymphocytes, and a unique TAF4b-containing TFIID was isolated from these cells (13). Moreover, during spermatogenesis, TAF7L-containing TFIID complexes have been found (48). Another set of human transcriptional regulatory multiprotein complexes containing TAFs are called TFTC, STAGA, or PCAF/GCN5 (6a, 36, 63). These complexes are functional homologues of the Saccharomyces cerevisiae SAGA complex, and all contain human homologues of the yeast histone acetyltransferase Gcn5 as well as a subset of SPT and ADA proteins, the 400-kDa TRRAP protein, and a number of TAFs (shared TAFs) also found in TFIID (36).TAF9 was first identified as a TFIID subunit from multiple organisms: human ( (44), and human TFTC-type complexes (10,36,67). Drosophila TAF9 has also been described in the Polycomb group complex and the e(y)2 protein-containing complex (17, 50).TAF9 was shown to interact directly with the tumor suppressor protein p53, the herpes simplex virus activator VP16, and the basal transcription factor TFIIB, and these interactions were suggested to be ...

Abnormal Sperm in Mice Lacking the Taf7l Gene

“…The chicken Taf7 gene, comprising 11 introns, is present on the region of chromosome 4 that is syntenic with the Taf7l-containing region of the mammalian X chromosome, indicating that the chicken Taf7 gene is orthologous to the mammalian Taf7l gene. Strikingly, the only other two X-linked TAF genes (TAF1 and TAF9B) in mammals both have autosomal homologues (TAF1L and TAF9) (15,40). Interestingly, the TAF1L gene is testis specific, arose by retroposition relatively recently in the old-world monkey lineage, including humans, and can functionally substitute the somatic TAF1 (40).…”

Core promoter recognition complex changes accompany liver development

“…Later spermatocytes were found to also express paralogous TAF7L that may cooperate with TBP and TAF1 in the regulation of spermatogenesis genes (5,6). Although unique paralogs of other canonical TAFs have been identified, their tissue-specific expression and functional significance remain to be elucidated (7). The finding that TAF8 is significantly up-regulated and may be required during adipogenesis is one of the few examples to date of a canonical TAF that is normally associated with TFIID but which may also have an independent developmental function (8).…”

New Insights into TAFs as Regulators of Cell Cycle and Signalling Pathways

“…Despite the high similarity between these two proteins, they are both required for cell viability and control the expression of distinct sets of genes. 16 The existence of these paralogues increases the complexity and combinatorial possibilities within the TFIID complex.…”