SPT5 licenses transition into productive transcription elongation by regulating promoter-proximal Pol II stability
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Elite
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Young Ah Goo
PROVIDER: MSV000086806 | MassIVE | Thu Feb 04 13:22:00 GMT 2021
SECONDARY ACCESSION(S): PXD023997
REPOSITORIES: MassIVE
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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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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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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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