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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TFIID, comprising the TATA box binding protein (TBP) and 13 TBP-associated factors (TAFs), plays a role in nucleation in the assembly of the RNA polymerase II preinitiation complexes on protein-encoding genes. TAFs are shared among other transcription regulatory complexes (e.g., SAGA, TBP-free TAF-containing complex [TFTC], STAGA, and PCAF/GCN5). Human TAF10, a subunit of both TFIID and TFTC, has three histone fold-containing interaction partners: TAF3, TAF8, and SPT7Like (SPT7L). In human cells, exogenously expressed TAF10 remains rather cytoplasmic and leptomycin B does not affect this localization. By using fluorescent fusion proteins, we show that TAF10 does not have an intrinsic nuclear localization signal (NLS) and needs one of its three interaction partners to be transported into the nucleus. When the NLS sequences of either TAF8 or SPT7L are mutated, TAF10 remains cytoplasmic, but a heterologous NLS can drive TAF10 into the nucleus. Experiments using fluorescence recovery after photobleaching show that TAF10 does not associate with any cytoplasmic partner but that once transported into the nucleus it binds to nuclear structures. TAF10 binding to importin beta in vitro is dependent on the coexpression of either TAF8 or TAF3, but not SPT7L. The cytoplasmic-nuclear transport of TAF10 is naturally observed during the differentiation of adult male germ cells. Thus, here we describe a novel role of the three mammalian interacting partners in the nuclear localization of TAF10, and our data suggest that a complex network of regulated cytoplasmic associations may exist among these factors and that this network is important for the composition of different TFIID and TFTC-type complexes in the nucleus.
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PMID:The nuclear import of TAF10 is regulated by one of its three histone fold domain-containing interaction partners. 1587 Feb 80

General transcription factor IID (TFIID) is a multisubunit protein complex involved in promoter recognition and is fundamental to the nucleation of the RNA polymerase II transcriptional preinitiation complex. TFIID is comprised of the TATA binding protein (TBP) and 12-15 TBP-associated factors (TAFs). While general transcription factors have been extensively studied in metazoans and yeast, little is known about the details of their structure and function in the plant kingdom. This work represents the first attempt to compare the structure of a plant TFIID complex with that determined for other organisms. While no TAF3 homolog has been observed in plants, at least one homolog has been identified for each of the remaining 14 TFIID subunits, including both TAF14 and TAF15 which have previously been shown to be unique to either yeast or humans. The presence of both TAFs 14 and 15 in plants suggests ancient roles for these proteins that were lost in metazoans and fungi, respectively. Yeast two-hybrid interaction assays resulted in a total of 65 binary interactions between putative subunits of Arabidopsis TFIID, including 26 contacts unique to plants. The interaction matrix of Arabidopsis TAFs is largely consistent with the three-lobed topological map for yeast TFIID, which suggests that the structure and composition of TFIID have been highly conserved among eukaryotes.
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PMID:Yeast two-hybrid map of Arabidopsis TFIID. 1734 43

Trimethylation of histone H3 at lysine 4 (H3K4me3) is regarded as a hallmark of active human promoters, but it remains unclear how this posttranslational modification links to transcriptional activation. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomic screening we show that the basal transcription factor TFIID directly binds to the H3K4me3 mark via the plant homeodomain (PHD) finger of TAF3. Selective loss of H3K4me3 reduces transcription from and TFIID binding to a subset of promoters in vivo. Equilibrium binding assays and competition experiments show that the TAF3 PHD finger is highly selective for H3K4me3. In transient assays, TAF3 can act as a transcriptional coactivator in a PHD finger-dependent manner. Interestingly, asymmetric dimethylation of H3R2 selectively inhibits TFIID binding to H3K4me3, whereas acetylation of H3K9 and H3K14 potentiates TFIID interaction. Our experiments reveal crosstalk between histone modifications and the transcription factor TFIID. This has important implications for regulation of RNA polymerase II-mediated transcription in higher eukaryotes.
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PMID:Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. 1788 55

Trimethylation of lysine residue K4 of histone H3 (H3K4me3) strongly correlates with active promoters for RNA polymerase II-transcribed genes. Several reader proteins, including the basal transcription factor TFIID, for this nucleosomal mark have been identified. Its TAF3 subunit specifically binds the H3K4me3 mark via its conserved plant homeodomain (PHD) finger. Here, we report the solution structure of the TAF3-PHD finger and its complex with an H3K4me3 peptide. Using a combination of NMR, mutagenesis, and affinity measurements, we reveal the structural basis of binding affinity, methylation-state specificity, and crosstalk with asymmetric dimethylation of R2. A unique local structure rearrangement in the K4me3-binding pocket of TAF3 due to a conserved sequence insertion underscores the requirement for cation-pi interactions by two aromatic residues. Interference by asymmetric dimethylation of arginine 2 suggests that a H3R2/K4 "methyl-methyl" switch in the histone code dynamically regulates TFIID-promoter association.
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PMID:Structural insight into the recognition of the H3K4me3 mark by the TFIID subunit TAF3. 1868 26

The RNA polymerase II core promoter is a structurally and functionally diverse transcriptional regulatory element. There are two main strategies for transcription initiation - focused and dispersed initiation. In focused initiation, transcription starts from a single nucleotide or within a cluster of several nucleotides, whereas in dispersed initiation, there are several weak transcription start sites over a broad region of about 50 to 100 nucleotides. Focused initiation is the predominant means of transcription in simpler organisms, whereas dispersed initiation is observed in approximately two-thirds of vertebrate genes. Regulated genes tend to have focused promoters, and constitutive genes typically have dispersed promoters. Hence, in vertebrates, focused promoters are used in a small but biologically important fraction of genes. The properties of focused core promoters are dependent upon the presence or absence of sequence motifs such as the TATA box and DPE. For example, Caudal, a key regulator of the homeotic gene network, preferentially activates transcription from DPE- versus TATA-dependent promoters. The basal transcription factors, which act in conjunction with the core promoter, are another important component in the regulation of gene expression. For instance, upon differentiation of myoblasts to myotubes, the cells undergo a switch from a TFIID-based transcription system to a TRF3-TAF3-based system. These findings suggest that the core promoter and basal transcription factors are important yet mostly unexplored components in the regulation of gene expression.
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PMID:Regulation of gene expression via the core promoter and the basal transcriptional machinery. 1968 82

The Transcription Factor IID is a large macromolecular complex composed of the TATA-box binding protein (TBP) and a group of 13-14 conserved TBP-associated factors (TAFs). TAFs are known to regulate transcription at various levels - mediating transcription via interaction with activators, histone modifications; recognition and binding to promoters; acting as a platform for other Transcription Factors and RNA polymerase II. Despite numerous previous studies of the TFIID complex, the knowledge concerning the structure of its components, and thus the exact mechanism of its function, remains undetermined. To carry out an in-depth analysis of TFIID we performed the structural bioinformatic analysis of the TFIID complex. The sequence identity and similarity of 13.74% and 37.56%, respectively (calculated with PAM250 matrix) between M1 aminopeptidase protein and TAF2 and the high similarity of their putative secondary structures allowed us to model a large part of the TAF2 structure. The sequence analysis enabled the mapping of previously not fully characterized structural domains in well-studied TAF proteins (including the full histone domains of TAF4 and 12 or TAF3 and 8). In this study we provided detailed structural models for all the elements of human analyzed in the context of TFIID activity, along with indications of structural alterations within TFIID in various animal model species.
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PMID:Structural bioinformatics of the general transcription factor TFIID. 2314 42