Institute of Human Genetics, UMR9002, CNRS and Univ. Montpellier, Montpellier, France.
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Nat Commun. 2020 Jun 4;11(1):2818. doi: 10.1038/s41467-020-16635-5.
In eukaryotes, trimethylation of lysine 9 on histone H3 (H3K9) is associated with transcriptional silencing of transposable elements (TEs). In drosophila ovaries, this heterochromatic repressive mark is thought to be deposited by SetDB1 on TE genomic loci after the initial recognition of nascent transcripts by PIWI-interacting RNAs (piRNAs) loaded on the Piwi protein. Here, we show that the nucleosome remodeler Mi-2, in complex with its partner MEP-1, forms a subunit that is transiently associated, in a MEP-1 C-terminus-dependent manner, with known Piwi interactors, including a recently reported SUMO ligase, Su(var)2-10. Together with the histone deacetylase Rpd3, this module is involved in the piRNA-dependent TE silencing, correlated with H3K9 deacetylation and trimethylation. Therefore, drosophila piRNA-mediated transcriptional silencing involves three epigenetic effectors, a remodeler, Mi-2, an eraser, Rpd3 and a writer, SetDB1, in addition to the Su(var)2-10 SUMO ligase.
在真核生物中，组蛋白 H3 赖氨酸 9 的三甲基化（H3K9）与转座元件（TEs）的转录沉默有关。在果蝇卵巢中，这种异染色质抑制标记被认为是由 SETDB1 在 PIWI 相互作用 RNA（piRNA）加载到 Piwi 蛋白上后对新生转录本的初始识别后，在 TE 基因组位点上沉积的。在这里，我们表明核小体重塑酶 Mi-2 与其伴侣 MEP-1 形成一个亚基，该亚基以 MEP-1 C 末端依赖性的方式与已知的 Piwi 相互作用蛋白短暂相关，包括最近报道的 SUMO 连接酶 Su(var)2-10。与组蛋白去乙酰化酶 Rpd3 一起，该模块参与了 piRNA 依赖性 TE 沉默，与 H3K9 去乙酰化和三甲基化相关。因此，果蝇 piRNA 介导的转录沉默除了 Su(var)2-10 SUMO 连接酶之外，还涉及三个表观遗传效应因子、一个重塑酶 Mi-2、一个擦除酶 Rpd3 和一个写入酶 SETDB1。
