PWWP2A variant NuRD complex represses intragenic spurious transcription initiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA624108 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11518805.fastq.gz | Fastqsanger.gz | |||
| SRR11518806.fastq.gz | Fastqsanger.gz | |||
| SRR11518807.fastq.gz | Fastqsanger.gz | |||
| SRR11518808.fastq.gz | Fastqsanger.gz | |||
| SRR11518809.fastq.gz | Fastqsanger.gz |
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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
Project description:Transcriptional fidelity depends on accurate promoter selection and initiation from the correct sites. In yeast, H3K36me3-mediated recruitment of the Rpd3S HDAC complex to gene bodies suppresses spurious transcription initiation. Here we describe an equivalent pathway in metazoans. PWWP2A/B is an H3K36me3 reader that forms a stable complex with HDAC1/2. We used CAGE-seq to profile all transcription initiation sites in wild-type mESCs and cells lacking PWWP2A/B. Loss of PWWP2A/B enhances spurious initiation from intragenic sites present in wild-type mESCs, and this effect is associated with increased levels of initiating Pol-II and histone acetylation. Spurious initiation events in Pwwp2a/b DKO mESCs do not overlap in genomic location or chromatin features with spurious sites that arise in Dnmt3b KO mESCs, previously reported to function in the suppression of intragenic transcriptional initiation, suggesting these pathways function cooperatively in maintaining the fidelity of transcription initiation in metazoans.
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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
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
Project description:Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as a direct histone variant H2A.Z interactor involved in mitosis and craniofacial development. Here, we identify the H2A.Z/PWWP2A-associated protein HMG20A as part of several chromatin-modifying complexes, including NuRD, andshow that it localizes to distinct genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis. Our data indicate that craniofacial malformations are caused by defects in neural crest cell (NCC) migration and cartilage formation. These developmental failures are phenocopied in Hmg20a-depleted mESCs, which show inefficient differentiation into NCCs and cardiomyocytes (CM). Consequently, loss of HMG20A, which marks open promoters and enhancers, results in chromatin accessibility changes and a striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and differentiation processes. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and reveal it as a key modulator of intricate developmental transcription programs that guide the differentiation of NCCs and CMs.
2023-03-11 | PXD038968 | Pride
Project description:Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as direct histone variant H2A.Z interactor involved in mitosis and cranial-facial development. Here, we identify the H2A.Z/PWWP2A-associated HMG20A protein as part of several chromatin-modifying complexes including NuRD, and to localize to genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis due to neural crest cell (NCC) and cardiomyocyte (CM) differentiation malfunctions. Such defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and CMs. Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and cardiac differentiation, thereby shedding light on HMG20A-specific developmental defects. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and as a key modulator during NCC and cardiomyocyte differentiation by guiding intricate developmental transcription programs.
2022-12-12 | GSE202196 | GEO
Project description:Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as direct histone variant H2A.Z interactor involved in mitosis and cranial-facial development. Here, we identify the H2A.Z/PWWP2A-associated HMG20A protein as part of several chromatin-modifying complexes including NuRD, and to localize to genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis due to neural crest cell (NCC) and cardiomyocyte (CM) differentiation malfunctions. Such defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and CMs. Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and cardiac differentiation, thereby shedding light on HMG20A-specific developmental defects. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and as a key modulator during NCC and cardiomyocyte differentiation by guiding intricate developmental transcription programs.
2022-12-12 | GSE202195 | GEO
Project description:Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as direct histone variant H2A.Z interactor involved in mitosis and cranial-facial development. Here, we identify the H2A.Z/PWWP2A-associated HMG20A protein as part of several chromatin-modifying complexes including NuRD, and to localize to genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis due to neural crest cell (NCC) and cardiomyocyte (CM) differentiation malfunctions. Such defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and CMs. Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and cardiac differentiation, thereby shedding light on HMG20A-specific developmental defects. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and as a key modulator during NCC and cardiomyocyte differentiation by guiding intricate developmental transcription programs.
2022-12-12 | GSE202198 | GEO
Project description:Specialized chromatin-binding proteins are required for DNA-based processes during development. We recently established PWWP2A as direct histone variant H2A.Z interactor involved in mitosis and cranial-facial development. Here, we identify the H2A.Z/PWWP2A-associated HMG20A protein as part of several chromatin-modifying complexes including NuRD, and to localize to genomic regulatory regions. Hmg20a depletion causes severe head and heart developmental defects in Xenopus laevis due to neural crest cell (NCC) and cardiomyocyte (CM) differentiation malfunctions. Such defects are pheno-copied in HMG20A-depleted mESCs, which show inefficient differentiation into NCCs and CMs. Accordingly, loss of HMG20A caused striking deregulation of transcription programs involved in epithelial-mesenchymal transition (EMT) and cardiac differentiation, thereby shedding light on HMG20A-specific developmental defects. Collectively, our findings implicate HMG20A as part of the H2A.Z/PWWP2A/NuRD-axis and as a key modulator during NCC and cardiomyocyte differentiation by guiding intricate developmental transcription programs.
2022-12-12 | GSE202197 | GEO
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 | GSE112112 | GEO