| Outline of Final Research Achievements |
Silencing of a subset of germline genes is dependent upon DNA methylation post-implantation. However, these genes are generally hypomethylated in the blastocyst, implicating alternative repressive pathways before implantation. Here, we show that in pre-implantation embryos, hypomethylated promoters of germline genes bound by PRC1.6 are enriched for RING1B-dependent H2AK119ub1 and H3K9me3. Accordingly, repression of these genes shows a greater dependence on PRC1.6 than DNA methylation. In contrast, germline genes are hypermethylated after implantation and their silencing is dependent upon SETDB1, PRC1.6/RING1B and DNA methylation, with H3K9me3. Thus, germline genes are initially repressed by PRC1.6, with DNA methylation subsequently engaged in post-implantation embryos.
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