TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing

TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing
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DOI:
10.1038/s41467-020-17372-5
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发表时间:
2020-07
影响因子:
16.6
通讯作者:
Theresa Schöpp;Ansgar Zoch;Rebecca V Berrens;Tania Auchynnikava;Y. Kabayama;L. Vasiliauskaitė;J. Rappsilber;R. Allshire;D. O’Carroll
Theresa Schöpp;Ansgar Zoch;Rebecca V Berrens;Tania Auchynnikava;Y. Kabayama;L. Vasiliauskaitė;J. Rappsilber;R. Allshire;D. O’Carroll
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Theresa Schöpp;Ansgar Zoch;Rebecca V Berrens;Tania Auchynnikava;Y. Kabayama;L. Vasiliauskaitė;J. Rappsilber;R. Allshire;D. O’Carroll

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PIWI蛋白MIWI2及其相关的PIWI相互作用RNA(PiRNAs)指示雄性生殖系中年轻的活性转座元件(TES)的DNA甲基化。PiRNAs被认为通过与新生转录物的碱基配对将MIWI2招募到转录活性的TE位点,但MIWI2用于指导新甲基化的下游机制和效应蛋白仍不完全清楚。在这里,我们发现MIWI2与胎儿生殖细胞中的TEX15相关。TEX15主要是一种核蛋白,它不是piRNA生物发生所必需的,但对于piRNA直接的从头开始甲基化和沉默是必不可少的。综上所述,TEX15是哺乳动物piRNA指导的DNA甲基化的重要执行者。
The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. piRNAs are proposed to recruit MIWI2 to the transcriptionally active TE loci by base pairing to nascent transcripts, however the downstream mechanisms and effector proteins utilized by MIWI2 in directing de novo TE methylation remain incompletely understood. Here, we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.