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Piwi-piRNA 复合物在靶位点诱导核构象的逐步变化。

Piwi-piRNA complexes induce stepwise changes in nuclear architecture at target loci.

机构信息

Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan.

Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Saitama, Japan.

出版信息

EMBO J. 2021 Sep 15;40(18):e108345. doi: 10.15252/embj.2021108345. Epub 2021 Aug 2.

DOI:10.15252/embj.2021108345
PMID:34337769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8441340/
Abstract

PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs that form effector complexes with PIWI proteins (Piwi-piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs). Drosophila Piwi transcriptionally silences specific targets through heterochromatin formation and increases histone H3K9 methylation (H3K9me3) and histone H1 deposition at these loci, with nuclear RNA export factor variant Nxf2 serving as a co-factor. Using ChEP and DamID-seq, we now uncover a Piwi/Nxf2-dependent target association with nuclear lamins. Hi-C analysis of Piwi or Nxf2-depleted cells reveals decreased intra-TAD and increased inter-TAD interactions in regions harboring Piwi-piRNA target TEs. Using a forced tethering system, we analyze the functional effects of Piwi-piRNA/Nxf2-mediated recruitment of piRNA target regions to the nuclear periphery. Removal of active histone marks is followed by transcriptional silencing, chromatin conformational changes, and H3K9me3 and H1 association. Our data show that the Piwi-piRNA pathway can induce stepwise changes in nuclear architecture and chromatin state at target loci for transcriptional silencing.

摘要

PIWI 相互作用 RNA（piRNA）是种系特异性的小 RNA，与 PIWI 蛋白形成效应复合物（Piwi-piRNA 复合物），通过抑制转座元件（TEs）在维持基因组完整性方面发挥着关键作用。果蝇 Piwi 通过异染色质形成转录沉默特定靶标，并增加这些基因座处的组蛋白 H3K9 甲基化（H3K9me3）和组蛋白 H1 沉积，核 RNA 输出因子变体 Nxf2 作为共因子。使用 ChEP 和 DamID-seq，我们现在发现 Piwi/Nxf2 依赖性靶标与核层粘连蛋白有关。Piwi 或 Nxf2 耗尽细胞的 Hi-C 分析显示，在含有 Piwi-piRNA 靶标 TEs 的区域中，TAD 内的相互作用减少，TAD 间的相互作用增加。使用强制固定系统，我们分析了 Piwi-piRNA/Nxf2 介导的 piRNA 靶区招募到核周的功能影响。随后去除活性组蛋白标记，随之而来的是转录沉默、染色质构象变化以及 H3K9me3 和 H1 结合。我们的数据表明，Piwi-piRNA 通路可以在靶基因座诱导核架构和染色质状态的逐步变化，从而实现转录沉默。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/99d3bf41b1ac/EMBJ-40-e108345-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/8484870c077a/EMBJ-40-e108345-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/7f40a7b5a556/EMBJ-40-e108345-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/0ec0bcfd4c4a/EMBJ-40-e108345-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/5316b158f88e/EMBJ-40-e108345-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/92eb91bc21e5/EMBJ-40-e108345-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/1e3cf8917190/EMBJ-40-e108345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/7db4ef25df19/EMBJ-40-e108345-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/982655e5d137/EMBJ-40-e108345-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/99d3bf41b1ac/EMBJ-40-e108345-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/8484870c077a/EMBJ-40-e108345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/d623f71794ed/EMBJ-40-e108345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/03d31eb0ee4d/EMBJ-40-e108345-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/7f40a7b5a556/EMBJ-40-e108345-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/0ec0bcfd4c4a/EMBJ-40-e108345-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/5316b158f88e/EMBJ-40-e108345-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/92eb91bc21e5/EMBJ-40-e108345-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/1e3cf8917190/EMBJ-40-e108345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/7db4ef25df19/EMBJ-40-e108345-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/982655e5d137/EMBJ-40-e108345-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be6f/8441340/99d3bf41b1ac/EMBJ-40-e108345-g009.jpg

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