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Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNA polymerase II general transcription factor TFIID is a macromolecular complex comprising the TATA-binding protein, TBP and 13-14 evolutionary conserved TBP-associated factors, TAFs. Although genetic experiments have shown that TAFs are essential for cell cycle progression in yeast and in rapidly proliferating vertebrate cells in vitro, new experiments indicate they may be dispensible in specific developmental and physiological processes. Moreover, the TAF4 subunit of TFIID negatively regulates proliferation by inhibiting activation of the TGFbeta signalling pathway by its paralogue TAF4b. TAF4 is however essential in the retinoic acid and cAMP signalling pathways acting as a cofactor for CREB and the retinoic acid receptor, but is a negative regulator of the ATF7 transcription factor.
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PMID:New insights into TAFs as regulators of cell cycle and signaling pathways. 1620 17

The androgen receptor (AR) is a member of the steroid receptor subfamily of nuclear receptors and is important for normal male sexual differentiation and fertility. The major transactivation function of the AR, termed activation function 1 (AF1), is modular in structure and has been mapped to the N terminus of the protein. To understand better the mechanisms whereby the AR activates transcription, we have established a novel cell-free transcription assay. This is based on the use of a dual reporter gene template, containing promoter proximal and distal G-less cassettes, which result in different size transcripts that can be easily detected and quantified. The promoter proximal transcript gives an indication of transcription initiation and promoter escape, whereas the relative levels of the distal transcript indicate elongation efficiency. The AR-AF1-Lex protein enhanced production of both transcripts whereas, in the absence of DNA binding, the AF1 domain squelched both initiation and elongation. Mutations in the transactivation domain that impaired transactivation and/or binding of the general transcription factor IIF (TFIIF) were found to reduce the ability of AR-AF1 to squelch transcription. Addition of recombinant TFIIF reversed squelching of the promoter-proximal but not the -distal G-less transcript, whereas addition of TATA-binding protein failed to reverse squelching of either transcript. Taken together, these results demonstrate that the AR N-terminal transactivation function, AF1, has the potential to regulate transcription at both the level of initiation and elongation, and that interactions with TFIIF are important during preinitiation complex assembly/open complex formation and/or promoter escape.
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PMID:The role of the general transcription factor IIF in androgen receptor-dependent transcription. 1664 39

TATA-binding protein-associated factor 1 (TAF1) is an essential component of the general transcription factor IID (TFIID), which nucleates assembly of the preinitiation complex for transcription by RNA polymerase II. TATA-binding protein and TAF1.TAF2 heterodimers are the only components of TFIID shown to bind specific DNA sequences (the TATA box and initiator, respectively), raising the question of how TFIID localizes to gene promoters that lack binding sites for these proteins. Here we demonstrate that Drosophila TAF1 protein isoforms TAF1-2 and TAF1-4 directly bind DNA independently of TAF2. DNA binding by TAF1 isoforms is mediated by cooperative interactions of two identical AT-hook motifs, one of which is encoded by an alternatively spliced exon. Electrophoretic mobility shift assays revealed that TAF1-2 bound the minor groove of adenine-thymine-rich DNA with a preference for the sequence AAT. Alanine-scanning mutagenesis of the alternatively spliced AT-hook indicated that Lys and Arg residues made essential DNA contacts, whereas Gly and Pro residues within the Arg-Gly-Arg-Pro core sequence were less important for DNA binding, suggesting that AT-hooks are more divergent than previously predicted. TAF1-2 bound with variable affinity to the transcription start site of several Drosophila genes, and binding to the hsp70 promoter was reduced by mutation of a single base pair at the transcription start site. Collectively, these data indicate that AT-hooks serve to anchor TAF1 isoforms to the minor groove of adenine-thymine-rich Drosophila gene promoters and suggest a model in which regulated expression of TAF1 isoforms by alternative splicing contributes to gene-specific transcription.
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PMID:DNA binding properties of TAF1 isoforms with two AT-hooks. 1689 81

Trypanosomatid parasites share a gene expression mode which differs greatly from that of their human and insect hosts. In these unicellular eukaryotes, protein-coding genes are transcribed polycistronically and individual mRNAs are processed from precursors by spliced leader (SL) trans splicing and polyadenylation. In trans splicing, the SL RNA is consumed through a transfer of its 5'-terminal part to the 5' end of mRNAs. Since all mRNAs are trans spliced, the parasites depend on strong and continuous SL RNA synthesis mediated by RNA polymerase II. As essential factors for SL RNA gene transcription in Trypanosoma brucei, the general transcription factor (GTF) IIB and a complex, consisting of the TATA-binding protein-related protein 4, the small nuclear RNA-activating protein complex, and TFIIA, were recently identified. Although T. brucei TFIIA and TFIIB are extremely divergent to their counterparts in other eukaryotes, their characterization suggested that trypanosomatids do form a class II transcription preinitiation complex at the SL RNA gene promoter and harbor orthologues of other known GTFs. TFIIH is a GTF which functions in transcription initiation, DNA repair, and cell cycle control. Here, we investigated whether a T. brucei TFIIH is important for SL RNA gene transcription and found that silencing the expression of the highly conserved TFIIH subunit XPD in T. brucei affected SL RNA gene synthesis in vivo, and depletion of this protein from extract abolished SL RNA gene transcription in vitro. Since we also identified orthologues of the TFIIH subunits XPB, p52/TFB2, and p44/SSL1 copurifying with TbXPD, we concluded that the parasite harbors a TFIIH which is indispensable for SL RNA gene transcription.
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PMID:Spliced leader RNA gene transcription in Trypanosoma brucei requires transcription factor TFIIH. 1725 43

Our current knowledge of the general factor requirement in transcription by the three mammalian RNA polymerases is based on a small number of model promoters. Here, we present a comprehensive chromatin immunoprecipitation (ChIP)-on-chip analysis for 28 transcription factors on a large set of known and novel TATA-binding protein (TBP)-binding sites experimentally identified via ChIP cloning. A large fraction of identified TBP-binding sites is located in introns or lacks a gene/mRNA annotation and is found to direct transcription. Integrated analysis of the ChIP-on-chip data and functional studies revealed that TAF12 hitherto regarded as RNA polymerase II (RNAP II)-specific was found to be also involved in RNAP I transcription. Distinct profiles for general transcription factors and TAF-containing complexes were uncovered for RNAP II promoters located in CpG and non-CpG islands suggesting distinct transcription initiation pathways. Our study broadens the spectrum of general transcription factor function and uncovers a plethora of novel, functional TBP-binding sites in the human genome.
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PMID:Identification of novel functional TBP-binding sites and general factor repertoires. 1726 53

Archaeal RNA polymerases (RNAPs) are most similar to eukaryotic RNAP II (Pol II) but require the support of only two archaeal general transcription factors, TBP (TATA-box binding protein) and TFB (archaeal homologue of the eukaryotic general transcription factor TFIIB) to initiate basal transcription. However, many archaeal genomes encode more than one TFB and/or TBP leading to the hypothesis that different TFB/TBP combinations may be employed to direct initiation from different promoters in Archaea. As a first test of this hypothesis, we have determined the ability of RNAP purified from Thermococcus kodakaraensis (T.k.) to initiate transcription from a variety of T.k. promoters in vitro when provided with T.k. TBP and either TFB1 or TFB2, the two TFBs encoded in the T.k. genome. With every promoter active in vitro, transcription initiation occurred with either TFB1 or TFB2 although the optimum salt concentration for initiation was generally higher for TFB2 (approximately 250 mM K(+)) than for TFB1 (approximately 200 mM K(+)). Consistent with this functional redundancy in vitro, T.k. strains have been constructed with the TFB1- (tfb1; TK1280) or TFB2- (tfb2; TK2287) encoding gene deleted. These mutants exhibit no detectable growth defects under laboratory conditions. Domain swapping between TFB1 and TFB2 has identified a central region that contributes to the salt sensitivity of TFB activity, and deleting residues predicted to form the tip of the B-finger region of TFB2 had no detectable effects on promoter recognition or transcription initiation but did eliminate the production of very short (< or =5 nt) abortive transcripts.
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PMID:TFB1 or TFB2 is sufficient for Thermococcus kodakaraensis viability and for basal transcription in vitro. 1727 36

Cellular regulatory networks are organized such that many proteins have few interactions, whereas a few proteins have many. These densely connected protein "hubs" are critical for the system-wide behavior of cells, and the capability of selectively perturbing a subset of interactions at these hubs is invaluable in deciphering and manipulating regulatory mechanisms. SELEX-generated RNA aptamers are proving to be highly effective reagents for inhibiting targeted proteins, but conventional methods generate one or several aptamer clones that usually bind to a single target site most preferred by a nucleic acid ligand. We advance a generalized scheme for isolating aptamers to multiple sites on a target molecule by reducing the ability of the preferred site to select its cognate aptamer. We demonstrate the use of this scheme by generating aptamers directed to discrete functional surfaces of the yeast TATA-binding protein (TBP). Previously we selected "class 1" RNA aptamers that interfere with the TBP's binding to TATA-DNA. By masking TBP with TATA-DNA or an unamplifiable class 1 aptamer, we isolated a new aptamer class, "class 2," that can bind a TBP.DNA complex and is in competition with binding another general transcription factor, TFIIA. Moreover, we show that both of these aptamers inhibit RNA polymerase II-dependent transcription, but analysis of template-bound factors shows they do so in mechanistically distinct and unexpected ways that can be attributed to binding either the DNA or TFIIA recognition sites. These results should spur innovative approaches to modulating other highly connected regulatory proteins.
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PMID:RNA aptamers directed to discrete functional sites on a single protein structural domain. 1736 Apr 23

TATA-binding protein (TBP) is essential for eukaryotic gene transcription. Human TBP contains a polymorphic polyglutamine (polyQ) domain in its N terminus and a DNA-binding domain in its highly conserved C terminus. Expansion of the polyQ domain to >42 glutamines typically results in spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder that resembles Huntington disease. Our recent studies have demonstrated that polyQ expansion causes abnormal interaction of TBP with the general transcription factor TFIIB and induces neurodegeneration in transgenic SCA17 mice (Friedman, M. J., Shah, A. G., Fang, Z. H., Ward, E. G., Warren, S. T., Li, S., and Li, X. J. (2007) Nat. Neurosci. 10, 1519-1528). However, it remains unknown how polyQ expansion influences DNA binding by TBP. Here we report that polyQ expansion reduces in vitro binding of TBP to DNA and that mutant TBP fragments lacking an intact C-terminal DNA-binding domain are present in transgenic SCA17 mouse brains. polyQ-expanded TBP with a deletion spanning part of the DNA-binding domain does not bind DNA in vitro but forms nuclear aggregates and inhibits TATA-dependent transcription activity in cultured cells. When this TBP double mutant is expressed in transgenic mice, it forms nuclear inclusions in neurons and causes early death. These findings suggest that the polyQ tract affects the binding of TBP to promoter DNA and that polyQ-expanded TBP can induce neuronal toxicity independent of its interaction with DNA.
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PMID:Polyglutamine expansion reduces the association of TATA-binding protein with DNA and induces DNA binding-independent neurotoxicity. 1821 37

The TATA-binding protein (TBP) is critical for transcription by all three nuclear RNA polymerases. In order to identify factors that interact with TBP, the nonnatural photoreactive amino acid rho-benzoyl-phenylalanine (BPA) was substituted onto the surface of Saccharomyces cerevisiae TBP in vivo. Cross-linking of these TBP derivatives in isolated transcription preinitiation complexes or in living cells reveals physical interactions of TBP with transcriptional coregulator subunits and with the general transcription factor TFIIA. Importantly, the results show a direct interaction between TBP and the SAGA coactivator subunits Spt3 and Spt8. Mutations on the Spt3-interacting surface of TBP significantly reduce the interaction of TBP with SAGA, show a corresponding decrease in transcription activation, and fail to recruit TBP to a SAGA-dependent promoter, demonstrating that the direct interaction of these factors is important for activated transcription. These results prove a key prediction of the model for stimulation of transcription at SAGA-dependent genes via Spt3. Our cross-linking data also significantly extend the known surfaces of TBP that directly interact with the transcriptional regulator Mot1 and the general transcription factor TFIIA.
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PMID:Site-specific cross-linking of TBP in vivo and in vitro reveals a direct functional interaction with the SAGA subunit Spt3. 1898 77

The general transcription factor TFIID is a macromolecular complex comprising the TATA-binding protein (TBP) and a set of 13-14 TBP associated factors (TAFs). This review discusses biochemical, genetic and electron microscopic data acquired over the past years that provide a model for the composition, organisation and assembly of TFIID. We also revisit ideas on how TFIID is recruited to the promoters of active and possibly repressed genes. Recent observations show that recognition of acetylated and methylated histone residues by structural domains in several TAFs plays an important role. Finally, we highlight several genetic studies suggesting that TFIID is required for initiation of transcription, but not for maintaining transcription once a promoter is in an active state.
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PMID:Recent advances in understanding the structure and function of general transcription factor TFIID. 1930 22


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