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H2A.Z reinforces maternal H3K4me3 formation and is essential for meiotic progression in mouse oocytes [RNA-Seq]

ABSTRACT: Mammalian oocytes establish a unique landscape of histone modifications, some of which are inherited by early embryos. How histone variants shape the maternal histone landscape remains unknown. Here, we map histone H2A variants in mouse fully grown oocytes (FGOs) and find that H2A.Z forms broad domains across intergenic regions, along non-canonical H3K4me3 (ncH3K4me3). During oocyte growth, H2A.Z progressively transitions from an active promoter-rich, canonical distribution to a non-canonical broad distribution (ncH2A.Z). Depletion of H2A.Z in oocytes partially impairs ncH3K4me3 formation and causes severe defects in meiotic progression, which resemble Mll2-knockout oocytes. Conversely, depletion of ncH3K4me3 by Mll2 knockout also causes a reduction of ncH2A.Z in FGOs. Thus, our study suggests that ncH2A.Z and ncH3K4me3 reinforce each other to form functional oocytes.

ORGANISM(S): Mus musculus

PROVIDER: GSE262049 | GEO | 2025/03/01

REPOSITORIES: GEO

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H2A.Z reinforces maternal H3K4me3 formation and is essential for meiotic progression in mouse oocytes

Project description:Mammalian oocytes establish a unique landscape of histone modifications, some of which are inherited by early embryos. How histone variants shape the maternal histone landscape remains unknown. Here, we map histone H2A variants in mouse fully grown oocytes (FGOs) and find that H2A.Z forms broad domains across intergenic regions, along non-canonical H3K4me3 (ncH3K4me3). During oocyte growth, H2A.Z progressively transitions from an active promoter-rich, canonical distribution to a non-canonical broad distribution (ncH2A.Z). Depletion of H2A.Z in oocytes partially impairs ncH3K4me3 formation and causes severe defects in meiotic progression, which resemble Mll2-knockout oocytes. Conversely, depletion of ncH3K4me3 by Mll2 knockout also causes a reduction of ncH2A.Z in FGOs. Thus, our study suggests that ncH2A.Z and ncH3K4me3 reinforce each other to form functional oocytes.

2025-03-01 | GSE262044 | GEO

H2A.Z regulates transcription, oocyte maturation and female fertility in mouse [ChIP-seq]

Project description:Histone variants differ from canonical histones in their ability to be incorporated into chromatin independently of S-phase. H2A.Z is an evolutionarily conserved histone variant that plays critical roles in transcription regulation. However, its roles during mammalian oogenesis, a unique developmental stage marked by dynamic transcription activity without DNA replication, remain elusive. In this study, we demonstrated that oocyte-specific depletion of H2A.Z results in profound epigenetic and transcriptional alterations, impeding oocyte meiosis II resumption in mice, causing female infertility. Mechanistically, H2A.Z in mouse oocytes is enriched at active promoters and enhancers. Interestingly, H2A.Z is depleted from CG-rich silenced promoters in fully-grown oocytes (FGOs), unlike that in growing oocytes, early embryos and mESCs. In FGOs, the presence of H2A.Z correlates with H3K27ac, except in regions with DNA methylation and H3K36me3. Depletion of H2A.Z leads to partial loss of H3K27ac at both promoters and enhancers, correlated with impaired gene expression. Consistent with a role in gene activation, H2A.Z in FGOs is widely acetylated at the promoters and enhancers. Together, our findings uncover an essential role of H2A.Z in oocyte maturation and activation of cis-regulatory elements.

2025-04-23 | GSE263818 | GEO

H2A.Z regulates transcription, oocyte maturation and female fertility in mouse [RNA-seq]

2025-04-23 | GSE263819 | GEO

Chromatin architecture organized by histone variants H3.3 and H2A.Z in the human genome

Project description:To understand how chromatin structure is organized by different histone variants, we have measured the genome-wide distribution of nucleosome core particles (NCPs) containing the histone variants H3.3 and H2A.Z in human cells. We find that a special class of NCPs containing both variants is enriched at ‘nucleosome-free regions’ of active promoters, enhancers and insulator regions. We show that preparative methods used previously in studying nucleosome structure result in the loss of these unstable double-variant NCPs. It seems likely that this instability facilitates the access of transcription factors to promoters and other regulatory sites in vivo. Other combinations of variants have different distributions, consistent with distinct roles for histone variants in the modulation of gene expression. genome-wide analysis of histone variants H2AZ, H3.3, and H3.3-H2A.Z double ChIP, plus input and genomic DNA controls in HeLa cells. H2A.Z samples are prepared under two different salt concentration conditions. (6 samples in total)

2009-07-26 | E-GEOD-13308 | biostudies-arrayexpress

A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme

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

Functional studies of a H2A.Bbd-like histone variant in mouse spermatogenesis

Project description:This SuperSeries is composed of the following subset Series: GSE29781: Expression data from 30do mouse spermatids [Affymetrix] GSE29913: Genome-wide distribution maps of histone variants H2A.Lap1 and H2A.Z in 30do mouse spermatids[ChIP_seq] Refer to individual Series

2012-01-20 | E-GEOD-29916 | biostudies-arrayexpress

Chromatin immunoprecipitation of wild type msc1D and swr1D fission yeast to determine genome-wide distribution of H2A.Z

Project description:Eukaryotic genomes are repetitively packaged into chromatin by nucleosomes, however they are regulated by the differences between nucleosomes, which establish various chromatin states. Replication-independent histone exchange could potentially perturb chromatin status if histone exchange chaperones, such as Swr1C, loaded histone variants into wrong sites. Here we use ChIP-chip analysis of H2A.Z-myc to show that in S.pombe, like S.cerevisiae, Swr1C is required for loading H2A.Z into specific sites, including the promoters of lowly expressed genes. However S.pombe Swr1C has an extra subunit, Msc1, which is a JumonjiC-domain protein of the Lid/Jarid1 family. The absence of Msc1 does not disrupt the S.pombe Swr1C or H2A.Z distribution in euchromatin. However in the absence of either Msc1 or Swr1 H2A.Z is ectopically found in the inner centromere and in subtelomeric chromatin. Normally this subtelomeric region, which appears to be a novel chromatin domain that we term ST-chromatin, not only lacks H2A.Z but also shows uniformly lower levels of H3K4me2, H4K5 and K12K5 acetylation than euchromatin. It also disproportionately contains the most lowly expressed genes during vegetative growth, including many meiotic-specific genes. These data describe H2A.Z distribution in S.pombe and identify a new mode of chromatin surveillance and maintenance based on negative regulation of histone variant misincorporation.

2009-11-09 | E-MEXP-1986 | biostudies-arrayexpress

Impact of Nucleosomal DNA Sequences on SWR Remodeler Activity and Histone H2A.Z Targeting

Project description:The variant histone H2A.Z is deposited into nucleosomes immediately downstream of promoters, where it plays a critical role in transcription. The site-specific deposition of H2A.Z is catalyzed by the SWR complex, a conserved chromatin remodeler with affinity for promoter-proximal nucleosome-depleted regions (NDRs) and histone acetylation. By comparing the genomic distribution of H2A.Z in wild-type and SWR-deficient cells, we found that SWR is also responsible for depositing H2A.Z at thousands of non-canonical sites not directly linked to NDRs or histone acetylation. To understand the targeting mechanism of H2A.Z, we presented SWR to a library of canonical nucleosomes isolated from yeast and analyzed the preferred substrates. Our results revealed that SWR preferentially deposited H2A.Z into a subset of endogenous H2A.Z sites, which are overrepresented by polyadenine tracks on the top strands of the DNA duplex at the nucleosomal entry-exit sites. Insertion of polyadenine sequences into recombinant nucleosomes near the outgoing H2A-H2B dimer enhanced SWR’s affinity for the nucleosomal substrate and increased its H2A.Z insertion activity. These findings suggest that the genome encodes sequence-based information that facilitates remodeler-mediated targeting of H2A.Z.

2024-01-13 | GSE252824 | GEO

Role of Dppa3 during primordial germ cell development II

Project description:We performed whole-genome bisulfite sequencing of Dppa3 knockout fully grown oocytes (FGOs).

2023-04-27 | GSE203204 | GEO

Genomic maps of homotypic H2Av, heterotypic H2Av, input and 80mM salt soluble chromatin from Drosophila S2 cells

Project description:Nucleosomes that contain the histone variant H2A.Z are enriched around transcriptional start sites in many organisms. A single octameric nucleosome can contain two H2A.Z histones (homotypic) or one H2A.Z and one canonical H2A (heterotype). We generated high-resolution maps of homotypic and heterotypic Drosophila H2A.Z (H2Av) nucleosomes. Although homotypic and heterotypic H2Av nucleosomes map throughout most of the genome, homotypic nucleosomes are enriched and heterotypic nucleosomes are depleted downstream of active promoters and intron/exon boundaries. The distribution of homotypic H2A.Z nucleosomes resembles that of salt-soluble nucleosomes and shows evidence of displacement during transcriptional elongation. Homotypic nucleosomes are also depleted downstream of paused polymerases, where salt-soluble nucleosomes are conspicuously depleted. Our results suggest a model whereby H2A.Z enrichment patterns result from different structural interactions within the core of heterotypic and homotypic nucleosomes following disruption during transcriptional elongation. We analyzed two replicates for input, heterotypic and homotypic purifications. We sequenced one library for each of the single H2Av pulldown and 80mM salt soluble samples.

2010-11-01 | E-GEOD-21615 | biostudies-arrayexpress

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