Project description:In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes, however the molecular mechanisms of this specificity remain unclear. Here we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in vivo, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long term epigenetic silencing during mammalian development.
Project description:In this study, we analysed early embryonic skin development (mus musculus; C57BL/6J) at the transcriptional level. Major questions concerned the cell type composition of early embryonic skin, and the emergence of transcriptional heterogeneity among epithelial and stromal precursor cells. Cells were isolated from embryonic dorsal skin and randomly sequenced (scRNA-Seq using 10X Genomics v2) without any cell sorting. Data from three embryonic time points (E12.5, E13.5, and E14.5) was integrated and compared to obtain a better understanding of the dynamics of early skin development.
Project description:Sperm contributes genetic and epigenetic information to the embryo to efficiently support development. However, the mechanism underlying such developmental competence remains elusive. Here, we investigated whether all sperm cells have a common epigenetic configuration that primes transcriptional program for embryonic development. We show for the first time that remodelling of histones during spermiogenesis results in the retention of methylated histone H3 at the same genomic location in every sperm cell. This homogeneously methylated fraction of histone H3 in the sperm genome is maintained during early embryonic replication. Such methylated histone fraction resisting postfertilisation reprogramming marks developmental genes whose expression is perturbed upon experimental reduction of histone methylation. A similar homogeneously methylated histone H3 fraction is detected in human sperm. Altogether, we uncover a conserved mechanism of paternal epigenetic information transmission to the embryo through the homogeneous retention of methylated histone in a sperm cells population.
Project description:Back skin from 8-10 weeks male mice was plucked to induce actively growing hair follicles. After 9 days, the back skin was irradiated with 5Gy ionizing radiation. Skin samples were collected for CHIP-seq analysis using a p53 antibody and H3K4me3 antibody. We compared wild type and Krt17 knock out mice for their epigenetic regulation of gene expression change in response to ionizing radiation
Project description:We performed ChIP-seq for H3K27me3 using dermal fibroblasts of E18.5 WT and Kdm6bKO mice. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for H3K27me3 Fibroblasts at various time points and one Kdm6bKO condition.