Pausing of RNA Polymerase II Disrupts DNA-Specified Nucleosome Organization to Enable Precise Gene Regulation

Gilchrist, Daniel A.; Santos, Gilberto dos; Fargo, David C.; Xie, Bin; Gao, Yuan; Li, Leping; Adelman, Karen

doi:10.1016/j.cell.2010.10.004

Cited by 389 publications

(581 citation statements)

References 50 publications

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“…Others have made similar suggestions; for example, paused Pol II has been argued to compete with histones for occupancy of highly regulated promoters in mammalian cells (71). To test the role of the PIC in histone eviction, we examined the effect of mutations in PIC components TBP and Pol II on histone association at various promoters.…”

Section: Discussionmentioning

confidence: 92%

Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast

Ansari

Paul

Sommer

et al. 2014

Journal of Biological Chemistry

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Background:Promoters of active genes in eukaryotes are typically depleted of histone proteins. Results: Histone eviction from the induced CHA1 promoter is compromised by mutations in transcription factors, and higher histone occupancy is also seen at constitutively active promoters in such mutants. Conclusion: Preinitiation complex formation promotes reduced histone occupancy at active gene promoters. Significance: Preinitiation complex components participate in chromatin remodeling.

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Section: Discussionmentioning

confidence: 92%

Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast

Ansari

Paul

Sommer

et al. 2014

Journal of Biological Chemistry

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“…129,130 Indeed, genes bound by DSIF and NELF significantly overlap (> 90%) with those bound by Pol II. 97,131,132 Finally, functional data supports this model, as incubation of HeLa cells with flavopiridol, an inhibitor of P-TEFb, reduces the level of transcription to a level strikingly similar to incubation with α-amanitin, a well-studied Pol II inhibitor. 133 Thus, P-TEFb-mediated DSIF/NELF release is a generally required and regulated step of transcription in higher eukaryotes.…”

Section: Pol II Elongation Is a General Step Of Transcription Regulatmentioning

confidence: 71%

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

Bowman

Kelly

2014

Nucleus

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“…Previous work showed that the transcription of these genes does not require CSB (24). The difference between these gene families may lie in the fact that stress-response gene promoters are preassembled, awaiting for a stimulus to start elongation, whereas NR-inducible and HK genes must undergo cycles or assembly and disassembly (24,29,30,(43)(44)(45).…”

Section: Sirt1 Mediates Repression Of Hk Genes In Xp-d/cs Cells After Uvmentioning

confidence: 99%

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells

Vélez-Cruz

Zadorin

Coin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Specific mutations in the XPD subunit of transcription factor IIH result in combined xeroderma pigmentosum (XP)/Cockayne syndrome (CS), a severe DNA repair disorder characterized at the cellular level by a transcriptional arrest following UV irradiation. This transcriptional arrest has always been thought to be the result of faulty transcription-coupled repair. In the present study, we showed that, following UV irradiation, XP-D/CS cells displayed a gross transcriptional dysregulation compared with "pure" XP-D cells or WT cells. Furthermore, global RNA-sequencing analysis showed that XP-D/CS cells repressed the majority of genes after UV, whereas pure XP-D cells did not. By using housekeeping genes as a model, we demonstrated that XP-D/CS cells were unable to reassemble these gene promoters and thus to restart transcription after UV irradiation. Furthermore, we found that the repression of these promoters in XP-D/CS cells was not a simple consequence of deficient repair but rather an active heterochromatinization process mediated by the histone deacetylase Sirt1. Indeed, RNA-sequencing analysis showed that inhibition of and/or silencing of Sirt1 changed the chromatin environment at these promoters and restored the transcription of a large portion of the repressed genes in XP-D/CS cells after UV irradiation. Our work demonstrates that a significant part of the transcriptional arrest displayed by XP-D/CS cells arises as a result of an active repression process and not simply as a result of a DNA repair deficiency. This dysregulation of Sirt1 function that results in transcriptional repression may be the cause of various severe clinical features in patients with XP-D/ CS that cannot be explained by a DNA repair defect.nucleotide excision repair | sirtuins | aging | progeria

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Pausing of RNA Polymerase II Disrupts DNA-Specified Nucleosome Organization to Enable Precise Gene Regulation

Cited by 389 publications

References 50 publications

Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast

Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

Sirt1 suppresses RNA synthesis after UV irradiation in combined xeroderma pigmentosum group D/Cockayne syndrome (XP-D/CS) cells

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