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The histone deacetylase SIRT6 restrains transcription elongation via promoter-proximal pausing

ABSTRACT: The histone deacetylase SIRT6 restrains transcription elongation via promoter-proximal pausing

PROVIDER: PRJNA540991 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9007580_1.fastq.gz	Fastqsanger.gz
	SRR9007580_2.fastq.gz	Fastqsanger.gz
	SRR9007590_1.fastq.gz	Fastqsanger.gz
	SRR9007590_2.fastq.gz	Fastqsanger.gz
	SRR9007600.fastq.gz	Fastqsanger.gz

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The histone deacetylase SIRT6 controls transcription elongation via promoter-proximal pausing (PRO-Seq)

Project description:Transcriptional regulation in eukaryotes commonly occurs at promoter-proximal regions wherein transcriptionally engaged RNA Polymerase II (Pol II) pauses before proceeding towards productive elongation. The roles of chromatin in this process remains poorly understood. Here, we demonstrate that the histone deacetylase SIRT6 regulates transcription elongation by binding to Pol II and anchoring the Negative ELongation Factor NELF, thereby preventing the release of Pol II towards elongation. Absence of SIRT6, or conditions of glucose deprivation, lead to increased levels of acetylated histone H3 at lysines 9 (H3K9ac) and 56 (H3K56ac), activation of the CDK9 kinase, phosphorylation of NELF and Pol II, and recruitment of the transcription factors MYC and BRD4, the PAF1 Complex, as well as several positive elongation factors, in turn releasing Pol II into productive elongation. Collectively, we identified SIRT6 as the first pausing-dedicated histone deacetylase, regulating intragenic H3K9ac and H3K56ac as critical chromatin modifications modulating transcriptional pausing and elongation.

2019-10-31 | GSE130691 | GEO

The histone deacetylase SIRT6 controls transcription elongation via promoter- proximal pausing (RNA-Seq)

2019-10-31 | GSE130690 | GEO

The histone deacetylase SIRT6 controls transcription elongation via promoter- proximal pausing (ChIP-Seq)

2019-10-31 | GSE130689 | GEO

The histone deacetylase SIRT6 controls transcription elongation via promoter- proximal pausing (RNA-Seq)

Project description:The histone deacetylase SIRT6 controls transcription elongation via promoter- proximal pausing (RNA-Seq)

| PRJNA540995 | ENA

The histone deacetylase SIRT6 controls transcription elongation via promoter- proximal pausing (ChIP-Seq)

Project description:The histone deacetylase SIRT6 controls transcription elongation via promoter- proximal pausing (ChIP-Seq)

| PRJNA540993 | ENA

The histone deacetylase SIRT6 controls transcription elongation via promoter-proximal pausing (PRO-Seq)

Project description:The histone deacetylase SIRT6 controls transcription elongation via promoter-proximal pausing (PRO-Seq)

| PRJNA540994 | ENA

The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing.

Project description:Transcriptional regulation in eukaryotes occurs at promoter-proximal regions wherein transcriptionally engaged RNA polymerase II (Pol II) pauses before proceeding toward productive elongation. The role of chromatin in pausing remains poorly understood. Here, we demonstrate that the histone deacetylase SIRT6 binds to Pol II and prevents the release of the negative elongation factor (NELF), thus stabilizing Pol II promoter-proximal pausing. Genetic depletion of SIRT6 or its chromatin deficiency upon glucose deprivation causes intragenic enrichment of acetylated histone H3 at lysines 9 (H3K9ac) and 56 (H3K56ac), activation of cyclin-dependent kinase 9 (CDK9)-that phosphorylates NELF and the carboxyl terminal domain of Pol II-and enrichment of the positive transcription elongation factors MYC, BRD4, PAF1, and the super elongation factors AFF4 and ELL2. These events lead to increased expression of genes involved in metabolism, protein synthesis, and embryonic development. Our results identified SIRT6 as a Pol II promoter-proximal pausing-dedicated histone deacetylase.

| S-EPMC6907403 | biostudies-literature

The histone deacetylase SIRT6 restrains transcription elongation via promoter-proximal pausing

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-10-31 | GSE130692 | GEO

Promoter proximal pausing and its regulation by c-Myc in embryonic stem cells

Project description:This SuperSeries is composed of the following subset Series: GSE20529: Promoter proximal pausing and its regulation by c-Myc in embryonic stem cells: ChIP-chip GSE20530: Promoter proximal pausing and its regulation by c-Myc in embryonic stem cells: ChIP-Seq Refer to individual Series

2010-04-14 | E-GEOD-20485 | biostudies-arrayexpress

GAGA Factor maintains promoters in nucleosome-free conformation and allows promoter-proximal pausing [MNase]

Project description:Promoter-proximal pausing of RNA polymerase II (Pol II) is a widespread in higher eukaryotes. Previous studies have shown that GAF is enriched at paused genes, but the role of GAF in pausing has not been well characterized on a genome-wide level. To investigate the role of GAF in pausing, we RNAi-depleted GAF from Drosophila S2 cells, and examined the effects on promoter-proximal polymerase. We confirmed the importance of GAF for pausing on the classic pause model gene Hsp70. To determine the dependence of pausing on GAF genome-wide, we assayed the levels of transcriptionally-engaged polymerase genome-wide using GRO-seq in control and GAF-RNAi cells. We found that promoter-proximal polymerase was significantly reduced on a subset of paused genes with GAF-bound promoters. There is a dramatic change in nucleosome distribution at genes with reduction in pausing upon GAF depletion and intergenic GAF binding sites in GAF knock-down, suggesting that GAF allows the establishment of pausing at these genes by directing nucleosome displacement off of the promoter. In addition, the insulator factor BEAF, BEAF-interacting protein Chriz, and transcription M1BP enrichment on unaffected genes suggests that redundant transcription factors or insulators protect other GAF-bound paused genes from GAF knock-down effects. Three biological replicates of MNase digested chromatin from LacZ-RNAi and GAGA factor-RNAi cells.

2015-04-04 | E-GEOD-58956 | biostudies-arrayexpress

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