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

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

PROVIDER: PRJNA540995 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9007610_1.fastq.gz	Fastqsanger.gz
	SRR9007610_2.fastq.gz	Fastqsanger.gz
	SRR9007611_1.fastq.gz	Fastqsanger.gz
	SRR9007611_2.fastq.gz	Fastqsanger.gz
	SRR9007612_1.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.

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

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

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

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

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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 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 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.

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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

PAF1, a molecular regulator of promoter-proximal pausing by RNA Polymerase II

Project description:The control of promoter-proximal pausing and the release of RNA polymerase II (RNA Pol II) is a widely used mechanism for regulating gene expression in metazoans, especially for genes that respond to environmental and developmental cues. Here, we identify Pol II associated Factor 1 (PAF1) as a major regulator of promoter-proximal pausing. Knockdown of PAF1 leads to increased release of paused Pol II into gene bodies at thousands of genes. Genes with the highest levels of paused Pol II exhibit the largest redistribution of Pol II from the promoter-proximal region into the gene body in the absence of PAF1. PAF1 depletion results in increased nascent transcription and increased levels of phosphorylation of Pol II’s c-terminal domain on serine 2 (Ser2P). These changes can be explained by the recruitment of the Ser2P kinase Super Elongation Complex (SEC) effecting increased release of paused Pol II into productive elongation, thus establishing a novel function for PAF1 as a major regulator of pausing in metazoans. ChIP-seq of Pol II of different forms, SEC subunits, PAFc subunits and H2Bub in human cell lines targeted by PAF1 or scramble shRNA. ChIP-seq of total Pol II in HCT116 cells targeted by BRE1A or scramble shRNA. ChIP-seq of total Pol II in S2 cells targeted by Paf1 or LacZ RNAi. Total RNA-seq, nascent RNA-seq and GRO-seq in HCT116 cells targeted by PAF1 or scramble shRNA.

2015-08-13 | E-GEOD-70408 | biostudies-arrayexpress

PAF1, a molecular regulator of promoter-proximal pausing by RNA Polymerase II

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