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Chromatin signature of embryonic pluripotency is established during zygotic genome activation [Danio rerio]

ABSTRACT: [PROJECT] After fertilization the embryonic genome is inactive until transcription is initiated during the maternal-zygotic transition (MZT). This universal process coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem (ES) cells. To study the changes in chromatin structure that accompany zygotic genome activation and pluripotency, we mapped the genomic locations of histone H3 modifications before and after MZT in zebrafish embryos. Repressive H3 lysine 27 trimethylation (H3K27me3) and activating H3 lysine 4 trimethylation (H3K4me3) are only detected after MZT. H3K4me3 marks more than 80% of genes, including many developmental regulatory genes that are also occupied by H3K27me3. Sequential chromatin immunoprecipitation demonstrates that both methylation marks occupy the same promoter regions, revealing that the bivalent chromatin domains found in cultured ES cells also exist in embryos. In addition, we find a large group of genes that are monovalently marked by H3K4me3 but not H3K27me3. These H3K4me3 monovalent genes are neither expressed nor stably bound by RNA polymerase II. Closer inspection of in vitro data sets reveals similar monovalent H3K4me3 domains in ES cells. The analysis of an inducible transgene indicates that H3K4me3 domains can form in the absence of sequence-specific transcriptional activators or stable association with RNA pol II. These results suggest that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during MZT. [SAMPLES] ChIPchip analysis of histone modifications (H3K4me3, H3K27me3, H3K36me3) and RNA polymerase II in pre MZT (256-cell) and post MZT (4hpf; dome/30% epiboly) wt zebrafish embryos.

ORGANISM(S): Danio rerio

PROVIDER: GSE20023 | GEO | 2010/01/26

SECONDARY ACCESSION(S): PRJNA124103

REPOSITORIES: GEO

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Project description:Epigenetic priming factors establish a permissive epigenetic landscape which is not required until a later developmental or physiological time point, temporally uncoupling the presence of these factors with their phenotypic effects. One classic example of epigenetic priming is in the context of bivalent chromatin, found in pluripotent stem cells and early embryos at key developmental gene promoters marked by both activating-associated H3K4me3 and repressive-associated H3K27me3 histone modifications. It is currently unknown how these bivalent domains are targeted, or precisely how they impact on lineage commitment. Here we show that the small heterodimerising non-enzymatic DNA binding proteins Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) act as epigenetic priming factors to establish bivalency at a subset of developmental genes. Dppa2/4 localise to the +1 nucleosome position of bivalent genes and while they are not required for pluripotency in embryonic stem cells (ESCs), double knockout cells fail to exit pluripotency and to differentiate efficiently, with delays in upregulating bivalently marked lineage genes. Proteomics reveal that Dppa2/4 interact on chromatin with members of the COMPASS and Polycomb complexes important for H3K4me3 and H3K27me3 deposition, respectively. Epigenetic profiling reveals a striking loss of H3K4me3, H3K27me3, and their associated enzymatic machinery at a significant subset of bivalent promoters in Dppa2/4 mutants, in addition to loss of H2A.Z and chromatin accessibility. In wild-type ESCs, these “Dppa2/4-dependent” bivalent promoters are characterised by low H3K4me3 enrichment and breadth, near-absent expression levels and initiating but not elongating RNA polymerase. Notably, Dppa2/4-dependent promoters are less evolutionarily conserved suggesting that they lack additional safeguard measures to maintain bivalency at these genes in the absence of Dppa2/4. Concomitantly with the loss of bivalency, Dppa2/4-dependent bivalent promoters gain DNA methylation and consequently are no longer able to be effectively activated upon ESC differentiation, leading to defects in cell fate acquisition. Our findings reveal a targeting principle for bivalency to developmental gene promoters poising them for future lineage specific gene activation.

Project description:The ability of cells to perceive and translate versatile cues into differential chromatin and transcriptional states is critical for many biological processes1-4. In plants, timely transition to a flowering state is crucial for successful reproduction5-7. EARLY BOLTING IN SHORT DAY (EBS) is a negative transcriptional regulator that prevents premature flowering in Arabidopsis8,9. Here, we revealed that bivalent bromo-adjacent homology (BAH)-plant homeodomain (PHD) reader modules of EBS bind H3K27me3 and H3K4me3, respectively. A subset of EBS-associated genes was co-enriched with H3K4me3, H3K27me3, and the Polycomb repressor complex 2 (PRC2). Interestingly, EBS adopts an auto-inhibition mode to mediate its binding preference switch between H3K27me3 and H3K4me3. This binding balance is critical because disruption of either EBS-H3K27me3 or EBS-H3K4me3 interaction induces EBS-mediated early floral transition. This study identifies a single bivalent chromatin reader capable of recognizing two antagonistic histone marks and reveals a distinct mechanism of interplay between active and repressive chromatin states.The ability of cells to perceive and translate versatile cues into differential chromatin and transcriptional states is critical for many biological processes1-4. In plants, timely transition to a flowering state is crucial for successful reproduction5-7. EARLY BOLTING IN SHORT DAY (EBS) is a negative transcriptional regulator that prevents premature flowering in Arabidopsis8,9. Here, we revealed that bivalent bromo-adjacent homology (BAH)-plant homeodomain (PHD) reader modules of EBS bind H3K27me3 and H3K4me3, respectively. A subset of EBS-associated genes was co-enriched with H3K4me3, H3K27me3, and the Polycomb repressor complex 2 (PRC2). Interestingly, EBS adopts an auto-inhibition mode to mediate its binding preference switch between H3K27me3 and H3K4me3. This binding balance is critical because disruption of either EBS-H3K27me3 or EBS-H3K4me3 interaction induces EBS-mediated early floral transition. This study identifies a single bivalent chromatin reader capable of recognizing two antagonistic histone marks and reveals a distinct mechanism of interplay between active and repressive chromatin states.v

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Chromatin signature of embryonic pluripotency is established during zygotic genome activation [Danio rerio]

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