生物
表观遗传学
DNA甲基化
染色质
遗传学
RNA导向的DNA甲基化
表观遗传学
基因组印记
印记(心理学)
计算生物学
细胞生物学
DNA
基因
基因表达
作者
Stefan Butz,Nina Schmolka,Ino D Karemaker,Rodrigo Villaseñor,Isabel Schwarz,Silvia Domcke,Esther C. H. Uijttewaal,Julian Jude,Florian Lienert,Arnaud R Krebs,Nathalie P. de Wagenaar,Bin Xue,Johannes Zuber,Ulrich Elling,Dirk Schübeler,Tuncay Baubec
出处
期刊:Nature Genetics
[Springer Nature]
日期:2022-11-01
卷期号:54 (11): 1702-1710
被引量:7
标识
DOI:10.1038/s41588-022-01210-z
摘要
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.
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