Project description:In this study, we knocked down Mfn1/H3.3 in mouse early embryos and examined their impact on transcriptome in mouse 8-cell embryos.
Project description:In this study, we knocked down Mfn1/H3.3 in mouse early embryos and examined their impact on DNA methylome in mouse 8-cell embryos.
2025-03-12 | GSE276710 | GEO
Project description:Impact of Mfn1 and H3.3 on DNA methylome in early mouse embryos
| PRJNA1157010 | ENA
Project description:Functions of histone crotonylation in early mouse embryos by ChIP-seq
Project description:Epigenetic reprogramming of the zygote involves dynamic incorporation of the histone variant, H3.3. However, the genome-wide distribution and dynamics of H3.3 during early development remain unknown. Here, we delineate the H3.3 landscapes in mouse oocytes and early embryos. We unexpectedly identify a non-canonical H3.3 pattern in mature oocytes and zygotes, in which local enrichment of H3.3 at active chromatin is suppressed and H3.3 is relatively evenly distributed across the genome. Interestingly, while the non-canonical H3.3 pattern forms gradually during oogenesis, it quickly switches to a canonical pattern at the 2-cell stage in a transcription-independent and replication-dependent manner. We find that incorporation of H3.1/H3.2 mediated by CAF-1 is a key process for the de novo establishment of the canonical pattern. Our data suggest that the presence of the non-canonical pattern and its timely transition toward a canonical pattern support the developmental program of early embryos.
Project description:Regions of H3.3 binding in WT and ATRX KO mouse ES cells were identified by ChIP seq Chip-seq experiements were performed in WT and ATRX KO E14 mouse ES cells
Project description:Zygotic gene activation (ZGA) is the first transcription event in life, and is associated with extensive epigenetic reprogramming, which is involved with dynamic incorporation of histone variant H3.3. H3.3 plays essential roles during mouse pre-implantation development. However, the coexistence of distinct sources of H3.3 in early embryos, including paternal and maternal allele-expressed H3.3 (paH3.3 and maH3.3), complicates our ability to track their individual dynamics, which may have distinct roles in embryonic development. In this study, by taking advantage of our H3.3B-HA-tagged mouse model, we illustrated the paH3.3 and maH3.3 landscapes in mouse early embryos, and described the manner of maternal mRNAs-derived H3.3 (mH3.3) on paternal genome reprogramming. We found the deposition of mH3.3 is required for cleavage development and minor ZGA, mechanistically, by mH3.3S31p-meditated acetylation at lysine 27. And, we propose that the mH3.3K27ac modification displaces the repressive histone modifications, thus enabling the activation of minor ZGA genes. Taken together, we demonstrate the central role of mH3.3 in reprogramming parental genomes by establishment of H3K27ac.
Project description:Polycomb repressive complex 2 (PRC2) regulates gene expression during lineage specification through trimethylation of lysine 27 on histone H3 (H3K27me3). In Drosophila, polycomb binding sites are dynamic chromatin regions coupled to incorporation of the histone variant H3.3. Here we show in mouse embryonic stem cells (ESCs) that H3.3 is required for proper establishment of H3K27me3 at the promoters of developmentally regulated genes. These promoters show reduced dynamics as determined by deposition of de novo synthesized histones, associated with reduced PRC2 occupancy. H3.3-depleted ESCs show upregulation of extraembryonic trophectoderm, as well as misregulation of other developmental genes upon differentiation. Our data demonstrate the importance of H3.3 incorporation in ESCs and suggest that changes in chromatin dynamics in its absence lead to misregulation of gene expression during differentiation. Moreover, our findings lend support to the emerging notion that H3.3 has multiple functions in distinct genomic locations that are not always correlated with an “active” chromatin state. Native ChIP analysis of three histone post-translational modifications (H3K4me3, H3K27me3, H3K27ac) in two mouse embryonic stem cell (ESC) lines (control and H3.3-depleted). Inputs sequenced as control. Native ChIP analysis of H3.3B-HA in control and Suz12-/- ESCs. Crosslinking ChIP analysis of histone H3 using a general H3 antibody in two ESC lines (control and H3.3-depleted). Crosslinking ChIP analysis Hira, UTX, and Jmjd3 in wild type and H3.3 KO ESCs.