Genome-wide maps of H3K27ac and H2A.Zac in HeLa K cells after depletion of PWWP2A by siRNA-mediated knockdown.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE110222 | GEO | 2018/08/27
REPOSITORIES: GEO
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Project description:Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified PWWP2A, which tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays we show that distinct domains of PWWP2A moreover mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly H3K36me3-containing gene bodies. Additionally, PWWP2A bind to an MTA1-specific core NuRD (M1HR) complex solely consisting of MTA1, HDAC1 and RBBP4/7, excluding CHD and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as an ever more complex chromatin binding protein serving as adapter for M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels and likely fine-tuning the transcriptional balance.
2018-08-27 | PXD010424 | Pride
Project description:The essential histone variant H2A.Z affects various DNA-based biological processes by so far not well understood mechanisms. Using a comprehensive label-free quantitative mass spectrometry-based approach we identified the human H2A.Z nucleosome interactome providing further insights into H2A.Z’s regulatory functions. Besides histone modification writer, eraser and reader complexes we identified PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A binds unprecedented strong to chromatin through a concerted multivalent binding mode. Two internal protein regions separately allow H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain mediates direct DNA binding. PWWP2A is found at euchromatic regions where it preferable binds to the H2A.Z-nucleosome-containing transcriptional start sites of transcribed genes. Cellular depletion of PWWP2A results in impaired proliferation caused by a mitotic delay likely due to deregulation of involved target genes. According with the strong cellular phenotype, knockdown of frog PWWP2A leads to severe developmental cranial facial defects arising from neural crest cell differentiation and migration problems. Together, this study identifies PWWP2A as an H2A.Z-specific multivalent chromatin binder and provides a novel link between H2A.Z, chromosome segregation and organ development.
2017-05-31 | GSE78003 | GEO
Project description:The essential histone variant H2A.Z affects various DNA-based biological processes by so far not well understood mechanisms. Using a comprehensive label-free quantitative mass spectrometry-based approach we identified the human H2A.Z nucleosome interactome providing further insights into H2A.Z’s regulatory functions. Besides histone modification writer, eraser and reader complexes we identified PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A binds unprecedented strong to chromatin through a concerted multivalent binding mode. Two internal protein regions separately allow H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain mediates direct DNA binding. PWWP2A is found at euchromatic regions where it preferable binds to the H2A.Z-nucleosome-containing transcriptional start sites of transcribed genes. Cellular depletion of PWWP2A results in impaired proliferation caused by a mitotic delay likely due to deregulation of involved target genes. According with the strong cellular phenotype, knockdown of frog PWWP2A leads to severe developmental cranial facial defects arising from neural crest cell differentiation and migration problems. Together, this study identifies PWWP2A as an H2A.Z-specific multivalent chromatin binder and provides a novel link between H2A.Z, chromosome segregation and organ development.
2017-05-31 | GSE78002 | GEO
Project description:Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified PWWP2A as a binder for H2A.Z-containing nucleosomes (Pünzeler, S. et al., EMBO J 2017). Here, as part of a larger project trying to characterize PWWP2A, we performed pulldowns using PWWP2A as a bait protein. Label-free quantitative mass spectrometry-based proteomics was used to detect and relatively quantify interaction partners of PWWP2A.
2018-08-30 | PXD010202 | 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 | 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: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: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