Hierarchical accumulation of histone variant H2A.Z regulates transcriptional states and histone modifications in early mammalian embryos
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ABSTRACT:
ORGANISM(S): Mus musculus Sus scrofa
PROVIDER: GSE188590 | GEO | 2022/06/24
REPOSITORIES: GEO
Similar Datasets
Project description:Early embryos undergo extensive epigenetic reprogramming to achieve gamete-to-embryo transition, which involves the loading and removal of histone variant H2A.Z on chromatin. However, how does H2A.Z regulate gene expression and histone modifications during preimplantation development remains unrevealed. Here, by using ultra-low-input native chromatin immunoprecipitation and sequencing, the genome-wide distribution of H2A.Z is delineated in mouse oocytes and early embryos. These landscapes indicate that paternal H2A.Z is removed upon fertilization, followed by unbiased accumulation on parental genomes during zygotic genome activation (ZGA). Remarkably, H2A.Z exhibits hierarchical accumulation as different peak types at promoters: promoters with double H2A.Z peaks are colocalized with H3K4me3 and indicate transcriptional activation; promoters with a single H2A.Z peak are more likely to occupy bivalent marks (H3K4me3+H3K27me3) and indicate development gene suppression; promoters with no H2A.Z accumulation exhibit persisting gene silencing in early embryos. Moreover, H2A.Z depletion changes the enrichment of histone modifications and RNA polymerase II binding at promoters, resulting in abnormal gene expression and developmental arrest during lineage commitment. Furthermore, similar transcription and accumulation patterns between mouse and porcine embryos indicate that a dual role of H2A.Z in regulating the epigenome required for proper gene expression is conserved during mammalian preimplantation development.
| S-EPMC9376818 | biostudies-literature
Project description:Early embryos undergo extensive epigenetic reprogramming to achieve gamete-to-embryo transition, which involves the loading and removal of histone variant H2A.Z on chromatin. Although the H2A.Z landscapes in sperm have been investigated, its dynamics during early development remain unrevealed. Here, by using ultra-low-input native chromatin immunoprecipitation and sequencing (ULI-NChIP-seq), we map the genome-wide distribution of H2A.Z in mouse oocytes and early embryos. We find that paternal H2A.Z is removed upon fertilization, followed by unbiased accumulation on parental genomes during zygotic genome activation (ZGA). More importantly, H2A.Z exhibits hierarchical accumulation as different peak types at promoters. We identify that double H2A.Z peaks co-localizes with H3K4me3 and facilitates transcriptional activation, bivalent markers (H3K4me3+H3K27me3) prefer to occupy single H2A.Z peak and inhibits developmental gene expression, while promoters with no H2A.Z accumulation exhibit gene silencing in early embryos. Remarkably, H2A.Z depletion changes the enrichments of histone modifications and RNA polymerase II (Pol II) binding at promoters, resulting in abnormal gene expression and developmental arrest during lineage commitment. Hence, H2A.Z plays dual roles in regulating the epigenomes required for proper gene expression during preimplantation development.
2022-06-24 | GSE188589 | GEO
Project description:Early embryos undergo extensive epigenetic reprogramming to achieve gamete-to-embryo transition, which involves the loading and removal of histone variant H2A.Z on chromatin. Although the H2A.Z landscapes in sperm have been investigated, its dynamics during early development remain unrevealed. Here, by using ultra-low-input native chromatin immunoprecipitation and sequencing (ULI-NChIP-seq), we map the genome-wide distribution of H2A.Z in mouse oocytes and early embryos. We find that paternal H2A.Z is removed upon fertilization, followed by unbiased accumulation on parental genomes during zygotic genome activation (ZGA). More importantly, H2A.Z exhibits hierarchical accumulation as different peak types at promoters. We identify that double H2A.Z peaks co-localizes with H3K4me3 and facilitates transcriptional activation, bivalent markers (H3K4me3+H3K27me3) prefer to occupy single H2A.Z peak and inhibits developmental gene expression, while promoters with no H2A.Z accumulation exhibit gene silencing in early embryos. Remarkably, H2A.Z depletion changes the enrichments of histone modifications and RNA polymerase II (Pol II) binding at promoters, resulting in abnormal gene expression and developmental arrest during lineage commitment. Hence, H2A.Z plays dual roles in regulating the epigenomes required for proper gene expression during preimplantation development.
2022-06-24 | GSE188588 | GEO
Project description:Hierarchical accumulation of histone variant H2A.Z regulates transcriptional states and histone modifications in early mammalian embryos
| PRJNA779463 | ENA
Project description:Hierarchical accumulation of histone variant H2A.Z regulates transcriptional states and histone modifications in early mammalian embryos [RNA-seq]
| PRJNA779466 | ENA
Project description:Hierarchical accumulation of histone variant H2A.Z regulates transcriptional states and histone modifications in early mammalian embryos [ChIP-seq]
| PRJNA779465 | ENA
Project description:During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development; still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z. H2A.Z enrichment precedes ZGA and RNA Polymerase II loading onto chromatin. In vivo knockdown of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that H2A.Z is essential for the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.
| S-EPMC8636486 | biostudies-literature
Project description:The histone variant H2A.Z has been implicated in many biological processes, such as gene regulation and genome stability. Here, we present the identification of H2A.Z.2.2 (Z.2.2), a novel alternatively spliced variant of histone H2A.Z and provide a comprehensive characterization of its expression and chromatin incorporation properties. Z.2.2 mRNA is found in all human cell lines and tissues with highest levels in brain. We show the proper splicing and in vivo existence of this variant protein in humans. Furthermore, we demonstrate the binding of Z.2.2 to H2A.Z-specific TIP60 and SRCAP chaperone complexes and its active replication-independent deposition into chromatin. Strikingly, various independent in vivo and in vitro analyses, such as biochemical fractionation, comparative FRAP studies of GFP-tagged H2A variants, size exclusion chromatography and single molecule FRET, in combination with in silico molecular dynamics simulations, consistently demonstrate that Z.2.2 causes major structural changes and significantly destabilizes nucleosomes. Analyses of deletion mutants and chimeric proteins pinpoint this property to its unique C-terminus. Our findings enrich the list of known human variants by an unusual protein belonging to the H2A.Z family that leads to the least stable nucleosome known to date.
| S-EPMC3401452 | biostudies-literature
Project description:Multiple lines of evidence implicate chromatin in the regulation of premessenger RNA (pre-mRNA) splicing. However, the influence of chromatin factors on cotranscriptional splice site usage remains unclear. Here we investigated the function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using the intron-rich model yeast Schizosaccharomyces pombe Using epistatic miniarray profiles (EMAPs) to survey the genetic interaction landscape of the Swr1 nucleosome remodeling complex, which deposits H2A.Z, we uncovered evidence for functional interactions with components of the spliceosome. In support of these genetic connections, splicing-specific microarrays show that H2A.Z and the Swr1 ATPase are required during temperature stress for the efficient splicing of a subset of introns. Notably, affected introns are enriched for H2A.Z occupancy and more likely to contain nonconsensus splice sites. To test the significance of the latter correlation, we mutated the splice sites in an affected intron to consensus and found that this suppressed the requirement for H2A.Z in splicing of that intron. These data suggest that H2A.Z occupancy promotes cotranscriptional splicing of suboptimal introns that may otherwise be discarded via proofreading ATPases. Consistent with this model, we show that overexpression of splicing ATPase Prp16 suppresses both the growth and splicing defects seen in the absence of H2A.Z.
| S-EPMC5411709 | biostudies-literature
Project description:BackgroundThe incorporation of histone variants into nucleosomes is one of the main strategies that the cell uses to regulate the structure and function of chromatin. Histone H2A.Z is an evolutionarily conserved histone H2A variant that is preferentially localized within nucleosomes at the transcriptional start site (TSS). H2A.Z reorganizes the local chromatin structure and recruits the transcriptional machinery for gene activation. High expression of H2A.Z has been reported in several types of cancers and is causally linked to genomic instability and tumorigenesis. However, it is not entirely clear how H2A.Z overexpression in cancer cells establishes aberrant chromatin states and promotes gene expression.ResultsThrough integration of genome-wide H2A.Z ChIP-seq data with microarray data, we demonstrate that H2A.Z is enriched around the TSS of cell cycle regulatory genes in bladder cancer cells, and this enrichment is correlated with the elevated expression of cancer-promoting genes. RNAi-mediated knockdown of H2A.Z in the cancer cells causes transcriptional suppression of multiple cell cycle regulatory genes with a distinct decrease in cell proliferation. H2A.Z nucleosomes around the TSS have higher levels of H3K4me2/me3, which coincides with the recruitment of two chromatin factors, WDR5 and BPTF. The observed recruitment is functional, as the active states of H2A.Z target genes are largely erased by suppressing the expression of WDR5 or BPTF, effects resembling H2A.Z knockdown.ConclusionsWe conclude that H2A.Z is overexpressed in bladder cancer cells and contributes to cancer-related transcription pathways. We also provide evidence in support of the engagement of H3K4me2/me3 and WDR5/BPTF in H2A.Z-induced cancer pathogenesis. Further studies are warranted to understand how H2A.Z overexpression contributes to the recruitment of the full repertoire of transcription machinery to target genes in bladder cancer cells.
| S-EPMC3853418 | biostudies-literature