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DNA序列和染色质修饰协同作用赋予印记控制区域的表观遗传双稳定性
作者:小柯机器人 发布时间:2022/11/7 20:29:40

瑞士苏黎世大学Tuncay Baubec团队近期取得重要工作进展,他们研究发现DNA序列和染色质修饰协同作用赋予印记控制区域的表观遗传双稳定性。相关研究成果2022年11月4日在线发表于《自然—遗传学》杂志上。

研究人员系统研究了这种表观遗传双稳定性的遗传和表观遗传决定因素。通过将ICR和相关DNA序列迭代整合到小鼠基因组中的异位位置,研究人员首先确定了维持胚胎干细胞表观遗传状态所需的DNA序列特征。ICR的自主调控特性进一步有助于创建DNA甲基化敏感报告子,并筛选参与调控其表观遗传记忆的关键成分。

除DNMT1、UHRF1和ZFP57外,研究人员还发现了阻止从甲基化状态转换为非甲基化状态的因素,并表明其中两个候选物ATF7IP和ZMYM2对胚胎干细胞ICR中DNA和H3K9甲基化的稳定性很重要。

据介绍,基因组印迹由印迹控制区(ICR)的亲本特异性DNA甲基化调控。尽管有相同的DNA序列,ICR能以两种不同的表观遗传状态存在,在无限的细胞分裂中被记忆,并在种系形成过程中被重置。

附:英文原文

Title: DNA sequence and chromatin modifiers cooperate to confer epigenetic bistability at imprinting control regions

Author: Butz, Stefan, Schmolka, Nina, Karemaker, Ino D., Villaseor, Rodrigo, Schwarz, Isabel, Domcke, Silvia, Uijttewaal, Esther C. H., Jude, Julian, Lienert, Florian, Krebs, Arnaud R., de Wagenaar, Nathalie P., Bao, Xue, Zuber, Johannes, Elling, Ulrich, Schbeler, Dirk, Baubec, Tuncay

Issue&Volume: 2022-11-04

Abstract: Genomic imprinting is regulated by parental-specific DNA methylation of imprinting control regions (ICRs). Despite an identical DNA sequence, ICRs can exist in two distinct epigenetic states that are memorized throughout unlimited cell divisions and reset during germline formation. Here, we systematically study the genetic and epigenetic determinants of this epigenetic bistability. By iterative integration of ICRs and related DNA sequences to an ectopic location in the mouse genome, we first identify the DNA sequence features required for maintenance of epigenetic states in embryonic stem cells. The autonomous regulatory properties of ICRs further enabled us to create DNA-methylation-sensitive reporters and to screen for key components involved in regulating their epigenetic memory. Besides DNMT1, UHRF1 and ZFP57, we identify factors that prevent switching from methylated to unmethylated states and show that two of these candidates, ATF7IP and ZMYM2, are important for the stability of DNA and H3K9 methylation at ICRs in embryonic stem cells.

DOI: 10.1038/s41588-022-01210-z

Source: https://www.nature.com/articles/s41588-022-01210-z

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex