High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation

Anandapadamanaban, Madhanagopal; Andrésen, Cecilia; Helander, Sara; Ohyama, Yoshifumi; Siponen, M.I.; Lundström, Patrik; Kokubo, Tetsuro; Ikura, Mitsuhiko; Moche, M.; Sunnerhagen, Maria

doi:10.1038/nsmb.2611

Cited by 73 publications

(98 citation statements)

References 58 publications

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“…Our results show that, upon degradation of Taf1, 2, 7, 11, or 13, the tested TFIID subunits (Tafs 1, 12, 3 and TBP) still co precipitated with Taf4, showing no obvious disruption in subunit association of the remaining TFIID complex. We note that ~2-fold lower levels of TBP co precipitated upon depletion of Taf1 or Taf11, which is expected since both subunits have been implicated in TBP binding (Anandapadamanaban et al, 2013; Lavigne et al, 1999; Shen et al, 2003). …”

Section: Resultssupporting

confidence: 54%

“…Next, the degron, auxin repressor protein IAA7, was integrated at the C-terminus of the TFIID-specific subunits Taf1, Taf2, Taf7, Taf11 and Taf13, (Cianfrocco et al, 2013; Hahn and Young, 2011; Leurent et al, 2004; 2002; Louder et al, 2016) (Fig 1A, left panel). Taf1, Taf11 and Taf13 have been implicated in TFIID-TBP binding (Anandapadamanaban et al, 2013; Lavigne et al, 1999; Shen et al, 2003). IAA7 was also fused to Med14, the Mediator subunit that connects the head, middle and tail modules (Plaschka et al, 2016; Tsai et al, 2014) with the reasoning that depletion of this subunit will inactivate Mediator.…”

Section: Resultsmentioning

confidence: 99%

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Transcription of Nearly All Yeast RNA Polymerase II-Transcribed Genes Is Dependent on Transcription Factor TFIID

et al. 2017

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SUMMARY Previous studies suggested that expression of most yeast mRNAs is dominated by either transcription factor TFIID or SAGA. We reexamined the role of TFIID by rapid depletion of S. cerevisiae TFIID subunits and measurement of changes in nascent transcription. We find that transcription of nearly all mRNAs is strongly dependent on TFIID function. Degron-dependent depletion of Tafs 1,2,7,11, and 13 showed similar transcription decreases for genes in the Taf1-depleted, Taf1-enriched, TATA-containing and TATA-less gene classes. The magnitude of TFIID-dependence varies with growth conditions, although this variation is similar genome-wide. Many studies have suggested differences in gene regulatory mechanisms between TATA and TATA-less genes and these differences have been attributed in part to differential dependence on SAGA or TFIID. Our work indicates that TFIID participates in expression of nearly all yeast mRNAs and that differences in regulation between these two gene categories is due to other properties.

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Section: Resultssupporting

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Transcription of Nearly All Yeast RNA Polymerase II-Transcribed Genes Is Dependent on Transcription Factor TFIID

et al. 2017

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“…All mutated residues except T112 and K218 directly contact either the bases or the backbone of TATA DNA. When TBP is not bound to TATA, its DNA binding surface can also interact with Mot1, an ATP-dependent regulator of TBP binding (53), or the TAND1 domain of the TFIID subunit Taf1 (54,55), or dimerize with another molecule of TBP (56). As detailed below (see Discussion), the phenotypes of our TBP mutations are distinct from those caused by mutations within Mot1, the Taf1 TAND1 domain, and disruption of TBP dimerization, so we believe that our TBP mutations exert their primary effects due to altered TBP-DNA binding.…”

Section: Resultsmentioning

confidence: 99%

Mutations on the DNA Binding Surface of TBP Discriminate between Yeast TATA and TATA-Less Gene Transcription

Kamenova

Warfield

Hahn

2014

Molecular and Cellular Biology

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, but analogous promoter elements have not been identified in Saccharomyces cerevisiae. We generated a set of mutations in the yeast TBP DNA binding surface and found that most support growth of yeast. Both in vivo and in vitro, many of these mutations are specifically defective for transcription of two TATA-containing genes with only minor defects in transcription of two TATA-less, TFIID-dependent genes. TBP binds several TATA-less promoters with apparent high affinity, but our results suggest that this binding is not important for transcription activity. Our results are consistent with the model that sequence-specific TBP-DNA contacts are not important at yeast TATA-less genes and suggest that other general transcription factors or coactivator subunits are responsible for recognition of TATA-less promoters. Our results also explain why yeast TBP derivatives defective for TATA binding appear defective in activated transcription. TATA binding protein (TBP) is an essential general transcription factor (GTF) required for eukaryotic nuclear and archaeal transcription (1, 2). TBP, in combination with a subset of RNA polymerase (Pol)-specific GTFs, is a component of the promoter recognition module in all TBP-dependent transcription systems (3, 4). In the RNA Pol II system, there are two general classes of core promoters: TATA-containing promoters with a close match to the consensus sequence TATAWAWR and TATA-less promoters lacking a close match (5-10). In Saccharomyces cerevisiae, ϳ15% of Pol II promoters are TATA-containing promoters and are generally highly regulated and/or stress-inducible genes (9, 10). TBP binds the TATA element with nanomolar affinity, interacting with the minor groove and bending DNA ϳ90°(11, 12). At yeast TATA-containing promoters, the TBP-TATA interaction is important for activity, and mutation of either the TBP binding surface or the TATA sequence severely decreases transcription initiation (13-16). DNA bending by TBP is essential for subsequent binding of the GTF TFIIB, as TFIIB binds both TBP and bent DNA on either side of TATA (17, 18).Yeast Pol II promoters have also been classified by dependence on the coactivators SAGA (Spt-Ada-Gcn5-acetyltransferase) and TFIID (transcription factor IID). Approximately 10% of promoters are primarily dependent on SAGA, while close to 90% are primarily TFIID dependent (19,20). TFIID-dependent promoters are generally TATA-less, and SAGA-dependent promoters are generally TATA-containing promoters. While these two coactivators have additional activities, they both play key roles in activator-dependent recruitment of TBP (21-24). In yeast, disruption of either SAGA or TFIID leads to reduced levels of promoter-associated TBP and preinitiation complex (PIC) formation (24-26).The roles of TBP in DNA recognition and transcription of TATA-less TFIID-dependent promoters are unclear. One widely supported model is that TFIID binding at metazoan TATA-less promoters is primarily driven by interaction of the TFIID Taf subunits with short degenerate promoter elements s...

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“…TFIID's inefficient DNA binding activity may be one way to prevent spurious basal expression of these stress response genes. TFIID/promoter interactions are likely repressed in part due to the presence of the TAF1 N-terminal domain (TAND), which occupies TBP's concave DNA binding surface (44)(45)(46)(47). This TAF1/TBP interaction is also thought to control the TFIID's global conformation to regulate promoter interactions.…”

Section: Discussionmentioning

confidence: 99%

p53 Dynamically Directs TFIID Assembly on Target Gene Promoters

Coleman

Qiao

Singh

et al. 2017

Molecular and Cellular Biology

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p53 is a central regulator that turns on vast gene networks to maintain cellular integrity in the presence of various stimuli. p53 activates transcription initiation in part by aiding recruitment of TFIID to the promoter. However, the precise means by which p53 dynamically interacts with TFIID to facilitate assembly on target gene promoters remains elusive. To address this key issue, we have undertaken an integrated approach involving single-molecule fluorescence microscopy, single-particle cryo-electron microscopy, and biochemistry. Our real-time single-molecule imaging data demonstrate that TFIID alone binds poorly to native p53 target promoters. p53 unlocks TFIID's ability to bind DNA by stabilizing TFIID contacts with both the core promoter and a region within p53's response element. Analysis of single-molecule dissociation kinetics reveals that TFIID interacts with promoters via transient and prolonged DNA binding modes that are each regulated by p53. Importantly, our structural work reveals that TFIID's conversion to a rearranged DNA binding conformation is enhanced in the presence of DNA and p53. Notably, TFIID's interaction with DNA induces p53 to rapidly dissociate, which likely leads to additional rounds of p53-mediated recruitment of other basal factors. Collectively, these findings indicate that p53 dynamically escorts and loads TFIID onto its target promoters. KEYWORDS p53, TFIID, transcription, structure, single-molecule microscopy M ore than 50% of cancer patients harbor p53 mutations, highlighting the essential role of this protein in tumor suppression (1). To properly maintain genomic stability, p53 induces vast gene networks involved in diverse cellular pathways, including the cell cycle arrest, apoptosis, and DNA repair pathways (2). In response to various stress stimuli, p53 acts as a transcriptional activator that specifically binds consensus response elements (REs; two 10-base-pair half-sites [RRRCWWGYYY]) within its target genes to directly stimulate gene expression (2). p53 utilizes its ability to nonspecifically bind and slide along the DNA to expedite the search for target REs (3). Upon recognition of its response genes, p53 facilitates transcription at least in part by targeting the TFIID-mediated transcription machinery to the promoter (4-7). TFIID is composed of TATA-binding protein (TBP) and 14 TBP-associated factors (TAFs). TFIID recognizes and binds multiple core promoter elements (e.g., the TATA box, the initiator, and downstream core promoter elements [DPE]) surrounding the transcription start site (TSS) (8). Once bound, TFIID serves as a central scaffold for six basal factors, including RNA polymerase II, to form a preinitiation complex (PIC) directing transcription initiation. Importantly, without the assistance of activators such as p53, TFIID's core promoter recognition is weak and rate limiting for transcription initiation due to inefficient PIC assembly (9-16). As TFIID is responsible for transcription of at least ϳ90% of proteincoding genes (17), unraveling how p...

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High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation

Cited by 73 publications

References 58 publications

Transcription of Nearly All Yeast RNA Polymerase II-Transcribed Genes Is Dependent on Transcription Factor TFIID

Transcription of Nearly All Yeast RNA Polymerase II-Transcribed Genes Is Dependent on Transcription Factor TFIID

Mutations on the DNA Binding Surface of TBP Discriminate between Yeast TATA and TATA-Less Gene Transcription

p53 Dynamically Directs TFIID Assembly on Target Gene Promoters

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