Morc1 reestablishes H3K9me3 heterochromatin on piRNA-targeted transposons in gonocytes

作者：Yuta Uneme, Ryu Maeda, Gen Nakayama, Haruka Narita, Naoki Takeda, Ryuji Hiramatsu, Hidenori Nishihara, Ryuichiro Nakato, Yoshiakira Kanai, Kimi Araki, Mikiko C. Siomi, Soichiro Yamanaka · 发表于：Proceedings of the National Academy of Sciences · 年份：2024 · DOI：10.1073/pnas.2317095121 · 被引用次数：15 · 研究领域：Chromosomal and Genetic Variations、CRISPR and Genetic Engineering、Genomics and Chromatin Dynamics

To maintain fertility, male mice re-repress transposable elements (TEs) that were de-silenced in the early gonocytes before their differentiation into spermatogonia. However, the mechanism of TE silencing re-establishment remains unknown. Here, we found that the DNA-binding protein Morc1, in cooperation with the methyltransferase SetDB1, deposits the repressive histone mark H3K9me3 on a large fraction of activated TEs, leading to heterochromatin. Morc1 also triggers DNA methylation, but TEs targeted by Morc1-driven DNA methylation only slightly overlapped with those repressed by Morc1/SetDB1-dependent heterochromatin formation, suggesting that Morc1 silences TEs in two different manners. In contrast, TEs regulated by Morc1 and Miwi2, the nuclear PIWI-family protein, almost overlapped. Miwi2 binds to PIWI-interacting RNAs (piRNAs) that base-pair with TE mRNAs via sequence complementarity, while Morc1 DNA binding is not sequence specific, suggesting that Miwi2 selects its targets, and then, Morc1 acts to repress them with cofactors. A high-ordered mechanism of TE repression in gonocytes has been identified.