Morc1 reestablishes H3K9me3 heterochromatin on piRNA- targeted transposons in gonocytes

• 成果类型: Article
• 署名作者: Uneme, Yuta; Maeda, Ryu; Nakayama, Gen; Narita, Haruka; Takeda, Naoki; Hiramatsu, Ryuji; Nishihara, Hidenori; Nakato, Ryuichiro; Kanai, Yoshiakira; Araki, Kimi; Siomi, Mikiko C.; Yamanaka, Soichiro
• 署名单位: University of Tokyo; University of Tokyo; Kumamoto University; University of Tokyo; Kindai University (Kinki University); University of Tokyo; Kumamoto University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8649
• DOI: 10.1073/pnas.2317095121
• 发表日期: 2024-03-26
• 关键词: embryonic stem-cells; primordial germ-cells; novo dna methylation; endogenous retroviruses; histone methyltransferase; open chromatin; genes; transcription; rna; ELEMENTS

摘要

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.