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卵巢缺失将 dLsd1 与 HP1a 连接起来,以实现局部 H3K4 去甲基化,这是异染色质基因沉默所必需的。

Ovaries absent links dLsd1 to HP1a for local H3K4 demethylation required for heterochromatic gene silencing.

机构信息

National Institute of Biological Sciences, Beijing, China.

Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.

出版信息

Elife. 2019 Jan 16;8:e40806. doi: 10.7554/eLife.40806.

Abstract

UNLABELLED

Heterochromatin Protein 1 (HP1) is a conserved chromosomal protein in eukaryotic cells that has a major role in directing heterochromatin formation, a process that requires co-transcriptional gene silencing mediated by small RNAs and their associated argonaute proteins. Heterochromatin formation requires erasing the active epigenetic mark, such as H3K4me2, but the molecular link between HP1 and H3K4 demethylation remains unclear. In a fertility screen in female , we identified (), which functions in the stem cell niche, downstream of Piwi, to support germline stem cell differentiation. Moreover, acts as a suppressor of position effect variegation, and is required for silencing telomeric transposons in the germline. Biochemically, Ova acts to link the H3K4 demethylase dLsd1 to HP1a for local histone modifications. Therefore, our study provides a molecular connection between HP1a and local H3K4 demethylation during HP1a-mediated gene silencing that is required for ovary development, transposon silencing, and heterochromatin formation.

EDITORIAL NOTE

This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

摘要

未标记

异染色质蛋白 1 (HP1) 是真核细胞中一种保守的染色体蛋白,在指导异染色质形成中起主要作用,该过程需要通过小 RNA 及其相关的 Argonaute 蛋白介导的共转录基因沉默。异染色质的形成需要消除活性表观遗传标记,如 H3K4me2,但 HP1 和 H3K4 去甲基化之间的分子联系尚不清楚。在雌性的生育力筛选中,我们鉴定了 (),它在干细胞巢中作为 Piwi 的下游因子,以支持生殖干细胞的分化。此外, 作为位置效应异染色质的抑制子,并且是生殖细胞中端粒转座子沉默所必需的。生化分析表明,Ova 可将 H3K4 去甲基酶 dLsd1 与 HP1a 连接起来,用于局部组蛋白修饰。因此,我们的研究提供了 HP1a 介导的基因沉默过程中 HP1a 与局部 H3K4 去甲基化之间的分子联系,这对于卵巢发育、转座子沉默和异染色质形成是必需的。

编辑注

本文经过编辑处理,作者决定如何处理同行评审中提出的问题。审稿人的评估是所有问题都已得到解决(见评审意见信)。

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