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主要卫星重复RNA通过RNA-核小体结合和RNA:DNA杂交形成来稳定Suv39h酶的异染色质保留。

Major satellite repeat RNA stabilize heterochromatin retention of Suv39h enzymes by RNA-nucleosome association and RNA:DNA hybrid formation.

作者信息

Velazquez Camacho Oscar, Galan Carmen, Swist-Rosowska Kalina, Ching Reagan, Gamalinda Michael, Karabiber Fethullah, De La Rosa-Velazquez Inti, Engist Bettina, Koschorz Birgit, Shukeir Nicholas, Onishi-Seebacher Megumi, van de Nobelen Suzanne, Jenuwein Thomas

机构信息

Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.

International Max Planck Research School for Molecular and Cellular Biology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.

出版信息

Elife. 2017 Aug 1;6:e25293. doi: 10.7554/eLife.25293.

DOI:10.7554/eLife.25293
PMID:28760199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5538826/
Abstract

The Suv39h1 and Suv39h2 histone lysine methyltransferases are hallmark enzymes at mammalian heterochromatin. We show here that the mouse Suv39h2 enzyme differs from Suv39h1 by containing an N-terminal basic domain that facilitates retention at mitotic chromatin and provides an additional affinity for major satellite repeat RNA. To analyze an RNA-dependent interaction with chromatin, we purified native nucleosomes from mouse ES cells and detect that Suv39h1 and Suv39h2 exclusively associate with poly-nucleosomes. This association was attenuated upon RNaseH incubation and entirely lost upon RNaseA digestion of native chromatin. Major satellite repeat transcripts remain chromatin-associated and have a secondary structure that favors RNA:DNA hybrid formation. Together, these data reveal an RNA-mediated mechanism for the stable chromatin interaction of the Suv39h KMT and suggest a function for major satellite non-coding RNA in the organization of an RNA-nucleosome scaffold as the underlying structure of mouse heterochromatin.

摘要

Suv39h1和Suv39h2组蛋白赖氨酸甲基转移酶是哺乳动物异染色质的标志性酶。我们在此表明，小鼠Suv39h2酶与Suv39h1不同，它含有一个N端碱性结构域，该结构域有助于其保留在有丝分裂染色质上，并对主要卫星重复RNA具有额外的亲和力。为了分析与染色质的RNA依赖性相互作用，我们从小鼠胚胎干细胞中纯化了天然核小体，并检测到Suv39h1和Suv39h2仅与多核小体相关联。这种关联在RNaseH孵育后减弱，在对天然染色质进行RNaseA消化后完全丧失。主要卫星重复转录本仍与染色质相关，并具有有利于RNA:DNA杂交形成的二级结构。这些数据共同揭示了一种RNA介导的机制，用于Suv39h组蛋白赖氨酸甲基转移酶与染色质的稳定相互作用，并表明主要卫星非编码RNA在作为小鼠异染色质基础结构的RNA-核小体支架组织中具有功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d3a/5538826/9881bef72f80/elife-25293-resp-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d3a/5538826/9881bef72f80/elife-25293-resp-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d3a/5538826/1c6fa5c1bea2/elife-25293-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d3a/5538826/6f2bdb0c8137/elife-25293-fig2.jpg
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