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Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269128 | GEO | 2024/06/13

REPOSITORIES: GEO

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Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [TT-seq]

Project description:Notch proteins undergo ligand-induced proteolysis to release a nuclear effector that influences a wide range of cell fate decisions by regulating gene activity. However, despite years of study, how Notch induces the transcription of its target genes remains unclear. Here, we comprehensively examined the response to human Notch1 across a time course of activation, using genomic assays of nascent RNA and chromatin accessibility. These data revealed that Notch induces target gene transcription primarily by releasing paused RNA polymerase II (RNAPII), in contrast to prevailing models suggesting that Notch acts by promoting chromatin accessibility. Indeed, we found that open chromatin is established at Notch-responsive regulatory elements prior to Notch signaling, through SWI/SNF-mediated remodeling. Notch activation, however, elicited no further chromatin opening at these loci. Together, these studies reveal that the nuclear response to Notch signaling is dictated by the pre-existing chromatin state and RNAPII distribution at the time of signal activation.

2024-06-13 | GSE269116 | GEO

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [PRO-seq]

2024-06-13 | GSE269115 | GEO

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [ChIP-seq]

2024-06-13 | GSE269113 | GEO

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [ATAC-seq]

2024-06-13 | GSE269112 | GEO

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility.

Project description:Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility.

| PRJNA1120361 | ENA

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [PRO-seq]

Project description:Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [PRO-seq]

| PRJNA1120338 | ENA

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [TT-seq]

Project description:Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [TT-seq]

| PRJNA1120341 | ENA

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [ChIP-seq]

Project description:Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [ChIP-seq]

| PRJNA1120336 | ENA

Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [ATAC-seq]

Project description:Notch induces transcription by stimulating release of paused RNA Pol II without increasing chromatin accessibility [ATAC-seq]

| PRJNA1120337 | ENA

Release of promoter-proximal paused Pol II in response to histone deacetylase inhibition.

Project description:A correlation between histone acetylation and transcription has been noted for a long time, but little is known about what step(s) in the transcription cycle is influenced by acetylation. We have examined the immediate transcriptional response to histone deacetylase (HDAC) inhibition, and find that release of promoter-proximal paused RNA polymerase II (Pol II) into elongation is stimulated, whereas initiation is not. Although histone acetylation is elevated globally by HDAC inhibition, less than 100 genes respond within 10 min. These genes are highly paused, are strongly associated with the chromatin regulators NURF and Trithorax, display a greater increase in acetylation of the first nucleosomes than other genes, and become transcriptionally activated by HDAC inhibition. Among these rapidly up-regulated genes are HDAC1 (Rpd3) and subunits of HDAC-containing co-repressor complexes, demonstrating feedback regulation upon HDAC inhibition. Our results suggest that histone acetylation stimulates transcription of paused genes by release of Pol II into elongation, and that increased acetylation is not a consequence of their enhanced expression. We propose that HDACs are major regulators of Pol II pausing and that this partly explains the presence of HDACs at active genes.

| S-EPMC7229826 | biostudies-literature

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