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A variant NuRD complex containing PWWP2A/B excludes MBD2/3 and directs HDAC activity to regulate histone acetylation and RNA Pol II dynamics at active genes

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

OTHER RELATED OMICS DATASETS IN: PXD010445

ORGANISM(S): Mus musculus

PROVIDER: GSE112114 | GEO | 2018/07/20

REPOSITORIES: GEO

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A variant NuRD complex containing PWWP2A/B excludes MBD2/3 and directs HDAC activity to regulate histone acetylation and RNA Pol II dynamics

Project description:Transcriptional regulation by chromatin is a highly dynamic process directed through the recruitment and coordinated action of epigenetic modifiers and readers of these modifications. Using an unbiased proteomic approach to find interactors of H3K36me3, a modification enriched on active chromatin, here we identify PWWP2A and HDAC2 among the top interactors. PWWP2A and its paralog PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66α/β, and CHD3/4. PWWP2A competes with MBD3 for binding to MTA1, thus defining a new variant NuRD complex that is mutually exclusive with the MBD2/3-containing NuRD. In mESCs, PWWP2A/B is most enriched at highly transcribed genes. Loss of PWWP2A/B leads to increases in histone acetylation predominantly at highly expressed genes, accompanied by decreases in Pol II elongation. Collectively, these findings suggest a role for PWWP2A/B in regulating transcription through the fine-tuning of histone acetylation dynamics at actively transcribed genes.

2018-07-20 | GSE112113 | GEO

A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes.

Project description: Not available

| S-EPMC6143588 | biostudies-literature

A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes

Project description:Transcriptional regulation by chromatin is a highly dynamic process directed through the recruitment and coordinated action of epigenetic modifiers and readers of these modifications. Using an unbiased proteomic approach to find interactors of H3K36me3, a modification enriched on active chromatin, we identify PWWP2A and HDAC2 among the top interactors. PWWP2A and its paralog PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66α/β, and CHD3/4. PWWP2A competes with MBD3 for binding to MTA1, thus defining a new variant NuRD complex that is mutually exclusive with the MBD2/3-containing NuRD. In mESCs, PWWP2A/B is most enriched at highly transcribed genes. Loss of PWWP2A/B leads to increases in histone acetylation predominantly at highly expressed genes, accompanied by decreases in Pol II elongation. Collectively, these findings suggest a role for PWWP2A/B in regulating transcription through the fine-tuning of histone acetylation dynamics at actively transcribed genes.

2018-07-19 | PXD010445 | Pride

A variant NuRD complex containing PWWP2A/B excludes MBD2/3 and directs HDAC activity to regulate histone acetylation and RNA Pol II dynamics

Project description:A variant NuRD complex containing PWWP2A/B excludes MBD2/3 and directs HDAC activity to regulate histone acetylation and RNA Pol II dynamics

| PRJNA439320 | ENA

A variant NuRD complex containing PWWP2A/B excludes MBD2/3 and directs HDAC activity to regulate histone acetylation and RNA Pol II dynamics at active genes

Project description:A variant NuRD complex containing PWWP2A/B excludes MBD2/3 and directs HDAC activity to regulate histone acetylation and RNA Pol II dynamics at active genes

| PRJNA439314 | ENA

PWWP2A variant NuRD complex represses intragenic spurious transcription initiation

Project description:H3 trimethylation at K36 deposited over the body of actively transcribed gene, is recognized by readers to modulate the epigenetic states, such as DNA methylation and histone deacetylation, to ensure the proper gene transcription. PWWP2A was identified as the reading component of variant NuRD complex to deacetylate gene bodies in mammalian cells. However, whether this deacetylation affects intragenic transcription is not investigated. Here, we performed CAGE-seq to profile transcription initiation in PWWP2A/B double knockout and fount that intragenic spurious transcription initiations at pre-existing low-level initiation from highly expressed genes were enhanced, accompanying with elevated acetylation level at H3K9 and H3K27, as well as nascent transcription. Additionally, the intragenic spurious transcriptions in PWWP2A/B loss are distinct with those in DNMT3B loss which is prone to produce de novo initiation and lack of PWWP2A/B-related chromatin changes. Collectively, PWWP2A/B-NuRD complex deacetylates active gene bodies to suppress intragenic spurious transcription in mammals.

2020-09-15 | GSE148382 | GEO

PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.

Project description: Not available

| S-EPMC6191444 | biostudies-literature

Histone variant H2A.Z deposition and acetylation directs the canonical Notch signaling response.

Project description: Not available

| S-EPMC6144792 | biostudies-literature

Disruption of the MBD2-NuRD complex but not MBD3-NuRD induces high level HbF expression in human adult erythroid cells.

Project description: Not available

| S-EPMC6959176 | biostudies-literature

p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex.

Project description: Not available