Gallus gallus
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ABSTRACT:
PROVIDER: PRJNA330725 | ENA |
REPOSITORIES: ENA
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Project description:The histone variant H2A.Z is one of the most evolutionally conserved histone variants. Here, we identified a cancer-associated mutation in H2A.Z and evaluate the mutation. Structural and biochemical in vitro analyses showed that the H2A.Z mutation destabilizes nucleosome containing it. Then we applied the genetic complementation analysis to analyze cellular functions of the H2A.Z mutant. Although the H2A.Z mutant is deposited into nucleosome and rescues the lethality of H2A.Z DKO cells, the mutant does not complement mitotic defects of H2A.Z DKO cells, suggesting that stability of H2A.Z nucleosome is required for proper mitotic progression. Importantly, the H2A.Z mutant led to mitotic defects even in the presence of a larger pool of wild-type H2A.Z. Thus, it is implicated that the cancer-associated mutation appeared in an allele of the H2A.Z isoform genes would be involved in carcinogenesis through causing mitotic defects.
2024-10-28 | GSE84647 | GEO
Project description:H2A.Z-nucleosomes participate in both euchromatic and heterochromatic scenarios and it has proven difficult to reveal correlation of the disparate roles with the stability features imparted by H2A.Z on the nucleosomes. Using a robust in situ assay of nucleosome stability and cell lines expressing only engineered forms of the variant we show that a major fraction of H2A.Z is released from the nucleosomes of peripheral heterochromatin at unusually high salt concentration, an observation reproduced with reconstituted nucleosomes. In cells expressing H2A.Z lacking its C-terminal tail, or upon addition of the tail peptide to control nuclei, canonical stability features are restored, the peripheral heterochromatin becomes dispersed and an increase of nuclease sensitivity, mainly at lamina-associated domains, ensues. Binding of the peptide to nucleosomes was detected by fluorescence correlation spectrometry. The peptide, when introduced into live cells, also induces reorganization of chromatin and decreases MYC expression, offering means for targeted epigenetic modulation.
2025-05-06 | PXD040998 | Pride
Project description:Nucleosome is a highly dynamic macromolecular complex that is assembled and remodeled by the replacement of major histone variant H2A.Z, thereby affecting nucleosome structure and stability.Here we established two cell lines stably overexpressing wild-type H2A.Z and mutant H2A.Z with ubiquitination deficiency to explore the potential effects caused by H2A.Z ubiquitination. Intriguingly, H2A.Z ubiquitination was first revealed to enhance the stability of H2A-H2A.Z heterotypic nucleosomes. Chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-Seq) further revealed that H2A.Z ubiquitination played a crucial role in the transcriptional regulation.
2021-06-30 | GSE178363 | GEO
Project description:The histone variant H2A.Z is one of the most evolutionally conserved histone variants. In vertebrates, two isoforms, H2A.Z.1 and H2A.Z.2, are identified and are involved in multiple epigenetic regulations. However, the role of H2A.Z in epigenetic regulations largely remains unknown especially in vertebrate. Previously, we derived tetracycline-inducible H2A.Z isofmrs double knockout (DKO) cells by using DT40 cells. With this cell, we showed that H2A.Z DKO leads to defects in mitotic progression and gene expression. To elucidate the function of H2A.Z further, we established genetic complementation system and confirmed that introducing exogenous H2A.Z complemented phenotypes of H2A.Z DKO cells. Given that acetylation of the N-terminal tail of H2A.Z reportedly contributes to significant roles in H2A.Z functions, we introduced two types of H2A.Z mutants, non-acetylable H2A.Z (5KR-H2A.Z) and chimeric H2A.Z in which its N-terminal tail is replaced with that of canonical H2A (H2A-H2A.Z), into H2A.Z DKO cells. These H2A.Z mutants complemented defects in mitotic progression. However, significant transcriptional dysregulation was observed in H2A.Z DKO cells stably expressing 5KR-H2A.Z and H2A-H2A.Z. These results suggest that the core domain and the N-terminal tail of the vertebrate H2A.Z contribute individually to mitotic progression and transcription regulation, respectively.
2017-08-21 | GSE70182 | 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 | 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:The histone variant macroH2A has been shown to generally associate with transcriptionally silent chromatin states. However, how macroH2A regulates the chromatin structure and functions in transcriptional process still remains elusive at the molecular level. In this study, we demonstrate that the incorporation of macroH2A does not affect the stability and the folding dynamics of nucleosome, but greatly impairs the FACT’s maintenance function at the nucleosome level. FACT can greatly impair the stability of macroH2A nucleosome, and quickly deplete the macroH2A nucleosome after the first unfolding process. Furthermore, we identify the key residue S139 of macroH2A, whose mutation can rescue the FACT’s function to maintain nucleosome integrity. Genome-wide analyses show that S139 mutation in macroH2A reshapes the position of macroH2A and regulates the stimulation-induced transcription in macrophage. Our findings provide mechanistic insights of how histone variant macroH2A coregulates with FACT at the nucleosome level and functions in cell response of macrophage in immunity.
2025-05-01 | GSE248551 | GEO
Project description:While it has been clearly established that well positioned H2A.Z-containing nucleosomes flank the nucleosome depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in trophoblast stem (TS) cells, the level of H2A.Z at promoters decreases during S phase coinciding with homotypic (H2A.Z/H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z/H2A). Surprisingly, these nucleosomes remain heterotypic at M phase. At the TSS, we identify an unstable heterotypic H2A.Z-containing nucleosome in G1 which, strikingly, is lost following DNA replication. These dynamic changes in H2A.Z at the TSS mirror a global expansion of the NDR at S and M which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of H2A.Z at promoters, it is targeted to the centromere when mitosis begins
2012-11-23 | GSE41371 | GEO
Project description:The histone variant H2A.Z plays key roles in gene expression, DNA repair, and centromere function. H2A.Z deposition is controlled by SWR-C chromatin remodeling enzymes that catalyze the nucleosomal exchange of canonical H2A with H2A.Z. Here we report that acetylation of histone H3 lysine 56 (H3-K56Ac) alters the substrate specificity of SWR-C, leading to promiscuous dimer exchange where either H2A.Z or H2A can be exchanged from nucleosomes. This result is confirmed in vivo, where genome-wide analysis demonstrates widespread decreases in H2A.Z levels in yeast mutants with hyperacetylated H3K56. Our work also suggests that a conserved SWR-C subunit may function as a M-bM-^@M-^\lockM-bM-^@M-^] that prevents removal of H2A.Z from nucleosomes. Our study identifies a histone modification that regulates a chromatin remodeling reaction and provides insights into how histone variants and nucleosome turnover can be controlled by chromatin regulators. H2A.Z ChIP seq experiments in mutants with constitutive H3K56ac
2013-04-15 | E-GEOD-43935 | biostudies-arrayexpress
Project description:While it has been clearly established that well positioned H2A.Z-containing nucleosomes flank the nucleosome depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in trophoblast stem (TS) cells, the level of H2A.Z at promoters decreases during S phase coinciding with homotypic (H2A.Z/H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z/H2A). Surprisingly, these nucleosomes remain heterotypic at M phase. At the TSS, we identify an unstable heterotypic H2A.Z-containing nucleosome in G1 which, strikingly, is lost following DNA replication. These dynamic changes in H2A.Z at the TSS mirror a global expansion of the NDR at S and M which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of H2A.Z at promoters, it is targeted to the centromere when mitosis begins We performed ChIP-Seq experiments (on mouse Trophoblast Stem cells arrested at G1; S and M stages of thecell cycle) using antibodies against histone variant H2A.Z and sequentional ChIP-re-ChIP-Seq experiments using H2A.Z antibody and H2A antibody in sequence. Combining those data sets with microarray gene expression expression data allowed us to see H2A.Z distribution over promoters of mouse coding genes in cell cycle dependant manner. Interestingly, Input also showed cell-cycle dependent effects, but histone H3 could be used as a cell-cycle independent normalisation factor. We also performed ChIP-seq with a CTCF pull-down to investigate its cell-cycle dependent relationship with heterochromatin.
2012-11-23 | E-GEOD-41371 | biostudies-arrayexpress