| Experiment Id | GSE149025 | Name | Role of E2F6 in gene expression and DNA methylation during mouse development |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-07-21 |
| description | In the mouse, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes in somatic cells, 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. Furthermore, inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Finally, we show that 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. We mapped E2F6 binding sites in mouse ES cells by ChIP-seq. We studied the role of E2F6 in gene expression by performing RNA-seq in triplicates in WT and E2f6-/- mouse ES cells and E8.5 embryos. To study the role of E2F6 in DNA methylation, we performed Whole Genome Bisulfite Sequencing (WGBS) in a WT and E2f6-/- embryo, as well as Reduced Representation Bisulfite Sequencing (RRBS) in WT and E2F6-/- ES cells, E8.5 embryos (two replicates), adult tissues (brain, muscle, kidney, three replicates), primary MEFs (two replicates) and MEF Crispr-Cas9 clones (two replicates). |
