Multiple direct interactions of TBP with the MYC oncoprotein

Wei, Yong; Resetca, Diana; Li, Zhe; Johansson-Åkhe, Isak; Ahlner, Alexandra; Helander, Sara; Wallenhammar, Amélie; Morad, Vivian; Raught, Brian; Wallner, Björn; Kokubo, Tetsuro; Tong, Yufeng; Penn, Linda Z.; Sunnerhagen, Maria

doi:10.1038/s41594-019-0321-z

Cited by 43 publications

(45 citation statements)

References 76 publications

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“…A TFIID requirement for RNAPII promoter-proximal pausing implies that other pause regulatory factors may function directly or indirectly through TFIID. Although additional mechanistic aspects remain to be addressed, it is notable that pause regulatory factors, including P-TEFb and MYC, interact (directly or indirectly) with TFIID (Gegonne et al, 2008;Wei et al, 2019;Yadav et al, 2019); moreover, TFIID is conformationally flexible (Cianfrocco et al, 2013) and likely undergoes structural reorganization during RNAPII transcription initiation and pause release (Yakovchuk et al, 2010;Zhang et al, 2015). Such structural transitions may contribute to TFIID-dependent regulation of RNAPII pausing.…”

Section: Discussionmentioning

confidence: 99%

TFIID Enables RNA Polymerase II Promoter-Proximal Pausing

et al. 2020

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TFIIH, Mediator, and RNAPII (Figure S1). Experiments were completed with the native human HSP70 promoter (HSPA1B gene), because others have shown that it is a quintessential model for promoter-proximal RNAPII pausing (Core et al., 2012). Because chromatin per se does not appear to be an essential regulator of RNAPII pausing in Drosophila or mammalian cells Lai and Pugh, 2017;Li et al., 2013), the in vitro transcription assays were completed on naked DNA templates (also see below).Using purified PIC factors, primer extension assays established that transcription initiation occurred at the annotated HSPA1B start site in vitro (Figure S2A), as expected. An overview of the transcription assay is shown in Figure 1A, which was based in part upon in vitro pausing assays with nuclear extracts (Marshall and Price, 1992;Qiu and Gilmour, 2017;Renner et al., 2001). Following PIC assembly, transcription was initiated by adding ATP, GTP, and UTP at physiologically relevant concentrations, with a low concentration of CTP, primarily 32 P-CTP. After one minute, reactions were chased with a physiologically relevant concentration of cold CTP and transcription was allowed to proceed for an additional nine minutes. These "pulse-chase" assays allow better detection of short (potentially paused) transcripts, which otherwise would be drowned out by elongated transcripts that invariably possess more incorporated 32 P-C bases. By directly labeling all transcripts with 32 P-CTP, the method is highly sensitive and allowed detection of transcripts of varied lengths; furthermore, the 32 P-CTP pulse-chase protocol ensured that 32 P-labeled transcripts resulted almost exclusively from single-round transcription (see Methods). Control experiments confirmed that transcripts detected were driven by the HSP70 promoter (e.g. not any contaminating nucleic acid) and that transcription was dependent on added PIC factors, as expected (Figure S2B).A variety of methods have established that RNAPII pauses after transcribing 20-80 bases in Drosophila and mammalian cells (

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Section: Discussionmentioning

confidence: 99%

TFIID Enables RNA Polymerase II Promoter-Proximal Pausing

et al. 2020

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“…Thus, factors that block TBP-DNA interactions are not universally repressive but instead may direct transcription from specific types of promoters. The MYC transcription factor was also shown to interact with the concave surface of TBP (Wei et al 2019). MYC is a well-studied transcription factor that activates transcription through mechanisms that remain incompletely understood (Rahl et al 2010).…”

Section: The Preinitiation Complex (Pic): a Universal Intermediate Inmentioning

confidence: 99%

Structure and mechanism of the RNA polymerase II transcription machinery

2020

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RNA polymerase II (Pol II) transcribes all protein-coding genes and many noncoding RNAs in eukaryotic genomes. Although Pol II is a complex, 12-subunit enzyme, it lacks the ability to initiate transcription and cannot consistently transcribe through long DNA sequences. To execute these essential functions, an array of proteins and protein complexes interact with Pol II to regulate its activity. In this review, we detail the structure and mechanism of over a dozen factors that govern Pol II initiation (e.g., TFIID, TFIIH, and Mediator), pausing, and elongation (e.g., DSIF, NELF, PAF, and P-TEFb). The structural basis for Pol II transcription regulation has advanced rapidly in the past decade, largely due to technological innovations in cryoelectron microscopy. Here, we summarize a wealth of structural and functional data that have enabled a deeper understanding of Pol II transcription mechanisms; we also highlight mechanistic questions that remain unanswered or controversial.

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“…These results, together with the heterogeneity in the cleft between SUPT3H, TADA1, and TRRAP, likely indicate a unique, highly dynamic mode of TBP binding by hSAGA, unlike that for the TFIID or the ySAGA complexes. The absence of Spt8 and the well characterized interaction of c-Myc with TBP ( 29 ) as well as TRRAP ( 10, 30 ) by separate c-Myc regions, might indicate that activators could play a role in TBP recruitment to metazoan SAGA. The ySAGA structure indicated that DNA binding by TBP is sterically hindered by Tra1 (homolog of human TRRAP) ( 16 ).…”

Section: Architecture Of Hsagamentioning

confidence: 99%

Structure of the human SAGA coactivator complex: The divergent architecture of human SAGA allows modular coordination of transcription activation and co-transcriptional splicing

Nogales

Herbst

Esbin

et al. 2021

Preprint

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Human SAGA is an essential co-activator complex that regulates gene expression by interacting with enhancer-bound activators, recruiting transcriptional machinery, and modifying chromatin near promoters. Subunit variations and the metazoan-specific requirement of SAGA in development hinted at unique structural features of the human complex. Our 2.9 Angstrom structure of human SAGA reveals intertwined functional modules flexibly connected to a core that distinctively integrates mammalian paralogs, incorporates U2 splicing subunits, and features a unique interface between the core and the activator-binding TRRAP. Our structure sheds light on unique roles and regulation of human coactivators with implications for transcription and splicing that have relevance in genetic diseases and cancer.

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Multiple direct interactions of TBP with the MYC oncoprotein

Cited by 43 publications

References 76 publications

TFIID Enables RNA Polymerase II Promoter-Proximal Pausing

TFIID Enables RNA Polymerase II Promoter-Proximal Pausing

Structure and mechanism of the RNA polymerase II transcription machinery

Structure of the human SAGA coactivator complex: The divergent architecture of human SAGA allows modular coordination of transcription activation and co-transcriptional splicing

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