Ovaries absent links dLsd1 to HP1a for local H3K4 demethylation required for heterochromatic gene silencing
Ovaries absent links dLsd1 to HP1a for local H3K4 demethylation required for heterochromatic gene silencing
复制标题
卵巢缺乏 dLsd1 与 HP1a 的链接，以实现异染色质基因沉默所需的局部 H3K4 去甲基化
DOI：
10.7554/elife.40806
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发表时间：
2019-01-16
期刊：
影响因子：
7.7
通讯作者：
Xi, Rongwen
中科院分区：
文献类型：
--
作者：
Yang, Fu;Quan, Zhenghui;Xi, Rongwen
异染色质蛋白1(HP1)是真核细胞中的一种保守的染色体蛋白，在异染色质的形成过程中起着重要的作用，这一过程需要小RNA及其相关Argavite蛋白介导的共转录基因沉默。异染色质的形成需要消除活跃的表观遗传标记，如H3K4me2，但HP1和H3K4去甲基化之间的分子联系尚不清楚。在雌性果蝇的生育筛查中，我们发现了无卵巢(OVA)，它位于Piwi下游的干细胞利基中，支持生殖系干细胞的分化。此外，OVA作为位置效应多样性的抑制者，对于沉默生殖系中的端粒转座子是必需的。在生物化学方面，OVA将H3K4去甲基酶dLsd1与HP1a连接起来，进行局部的组蛋白修饰。因此，我们的研究提供了HP1a与H3K4去甲基化之间的分子联系，HP1a介导的基因沉默是卵巢发育、转座子沉默和异染色质形成所必需的。编者按：本文经过编辑过程，作者决定如何对同行审查期间提出的问题作出回应。审查编辑的评估是，所有问题都已得到解决(见决定函)。
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 Drosophila, we identified ovaries absent (ova), which functions in the stem cell niche, downstream of Piwi, to support germline stem cell differentiation. Moreover, ova 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).