Piwi Modulates Chromatin Accessibility by Regulating Multiple Factors Including Histone H1 to Repress Transposons
Piwi Modulates Chromatin Accessibility by Regulating Multiple Factors Including Histone H1 to Repress Transposons
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DOI：
10.1016/j.molcel.2016.06.008
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发表时间：
2016-08-04
期刊：
影响因子：
16
通讯作者：
Saito, Kuniaki
中科院分区：
文献类型：
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作者：
Iwasaki, Yuka W.;Murano, Kensaku;Saito, Kuniaki
PIWI相互作用RNA（piRNA）介导动物性腺中转座因子（TE）的转录和转录后沉默。在果蝇卵巢中，Piwi-piRNA复合物（Piwi-piRISC）通过修饰染色质状态（例如通过H3 K9三甲基化）来抑制TE转录。在这里，我们证明了Piwi与连接体组蛋白H1的物理相互作用。Piwi的耗竭降低了TE子集的H1密度，导致其去阻遏。在这些位点的沉默分别需要H1和H3 K9 me 3和异染色质蛋白1a（HP 1a）。H1的缺失增加了靶基因座的染色质可及性，而不影响这些基因座的H3 K9 me 3密度，而HP 1a的缺失不影响H1密度。因此，Piwi-piRISC需要H1和HP 1a来抑制TE，并且沉默与染色质状态而不是H3 K9 me 3标记相关。这些发现表明，Piwi-piRISC调节染色质组分与靶基因座的相互作用，以通过调节染色质可及性来维持TE的沉默。
PIWI-interacting RNAs (piRNAs) mediate transcriptional and post-transcriptional silencing of transposable element (TE) in animal gonads. In Drosophila ovaries, Piwi-piRNA complexes (Piwi-piRISCs) repress TE transcription by modifying the chromatin state, such as by H3K9 trimethylation. Here, we demonstrate that Piwi physically interacts with linker histone H1. Depletion of Piwi decreases H1 density at a subset of TEs, leading to their derepression. Silencing at these loci separately requires H1 and H3K9me3 and heterochromatin protein 1a (HP1a). Loss of H1 increases target loci chromatin accessibility without affecting H3K9me3 density at these loci, while loss of HP1a does not impact H1 density. Thus, Piwi-piRISCs require both H1 and HP1a to repress TEs, and the silencing is correlated with the chromatin state rather than H3K9me3 marks. These findings suggest that Piwi-piRISCs regulate the interaction of chromatin components with target loci to maintain silencing of TEs through the modulation of chromatin accessibility.