In mammals, facultative heterochromatin has a crucial role in regulating gene expression for their proper development (e.g., X-chromosome inactivation). Its chromatin state is maintained by a specialized machinery which gets activated during S-phase in proliferating cells. However, in cell cycle arrested gonocyte, which are embryonic male germ cells, how its chromatin state is reorganized after the global reprogramming event is mostly unclear. We have discovered that transient opening of large transposon-rich heterochromatin regions with several mega-basse in size, termed DADs (short for differentially accessible domains), in gonocyte, together with the rewriting of major histone marks, suggesting that these regions are novel facultative heterochromatin. Moreover, the global 3D chromosome organization is untangled, leading to relaxed chromatin state which accepts the genome wide de novo DNA methylation. The Piwi-piRNA pathway induces local chromatin compaction on a fraction of TEs within open DADs, forming a complex regulatory network for these genomic parasites in gonocyte.
These data support a model in which, although it is counterintuitive, the Piwi–piRNA pathway initially represses de novo DNA methylation by inducing local chromatin compaction within DADs, which leads to delalyed DNA methylation on piRNA-target TEs in gonocyte.