代际维持的组蛋白H4第16位赖氨酸乙酰化影响子代

添加时间:2020-06-08 浏览数:

本期文章:《细胞》:Online/在线发表

德国马克斯普朗克研究所Asifa Akhtar研究组的一项最新研究发现,代际维持的组蛋白H4第16位赖氨酸乙酰化影响子代的基因激活。这一研究成果于2020年6月4日在线发表在《细胞》上。

研究人员发现,在果蝇和哺乳动物中,从卵母细胞到受精胚胎的组蛋白H4第16位赖氨酸乙酰化(H4K16ac)得以维持。H4K16ac形成大的区域,可控制果蝇中合子基因组激活(ZGA)之前启动子的核小体可及性。引起H4K16ac丢失的MOF乙酰转移酶母源敲低会导致异常的RNA Pol II募集,损害ZGA期间活性基因组区室的3D组织,并导致合子后基因表达的下调。

 

组蛋白去乙酰基酶的生殖敲低表明,其他乙酰化标记不能补偿卵母细胞中H4K16ac的丢失。此外,MOF的合子重新表达既不能恢复胚胎活力,也不能恢复X染色体剂量补偿。因此,母源H4K16ac为后代提供了指导功能,可引起子代的基因激活。

 

据了解,在ZGA之前,静态基因组经过重新编程以过渡到转录活性状态。然而,目前尚不清楚早期胚胎发生过程中常染色质建立的机制。

 

附:英文原文

Title: Intergenerationally Maintained Histone H4 Lysine 16 Acetylation Is Instructive for Future Gene Activation

Author: Maria Samata, Anastasios Alexiadis, Gautier Richard, Plamen Georgiev, Johannes Nuebler, Tanvi Kulkarni, Gina Renschler, M. Felicia Basilicata, Fides Lea Zenk, Maria Shvedunova, Giuseppe Semplicio, Leonid Mirny, Nicola Iovino, Asifa Akhtar

Issue&Volume: 2020-06-04

Abstract: Before zygotic genome activation (ZGA), the quiescent genome undergoes reprogrammingto transition into the transcriptionally active state. However, the mechanisms underlyingeuchromatin establishment during early embryogenesis remain poorly understood. Here,we show that histone H4 lysine 16 acetylation (H4K16ac) is maintained from oocytesto fertilized embryos in Drosophila and mammals. H4K16ac forms large domains that control nucleosome accessibility ofpromoters prior to ZGA in flies. Maternal depletion of MOF acetyltransferase leadingto H4K16ac loss causes aberrant RNA Pol II recruitment, compromises the 3D organizationof the active genomic compartments during ZGA, and causes downregulation of post-zygoticallyexpressed genes. Germline depletion of histone deacetylases revealed that other acetylmarks cannot compensate for H4K16ac loss in the oocyte. Moreover, zygotic re-expressionof MOF was neither able to restore embryonic viability nor onset of X chromosome dosagecompensation. Thus, maternal H4K16ac provides an instructive function to the offspring,priming future gene activation.

DOI: 10.1016/j.cell.2020.05.026

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30621-8

期刊信息

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216

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