数字农科院2.0

KDM2A and KDM2B protect a subset of CpG islands from DNA methylation

文献类型： 外文期刊

作者： Liu, Yuan;Liu, Ying;Zhu, Yunji;Hu, Di;Nie, Hu;Xie, Yali;Sun, Rongrong;He, Jin;Zhang, Honglian;Lu, Falong

作者机构：

关键词： KDM2A;KDM2B;CpG island;DNA methylation;Demethylation;Embryonic stem cell

期刊名称： JOURNAL OF GENETICS AND GENOMICS

ISSN： 1673-8527

年卷期： 2025 年 52 卷 1 期

页码：

收录情况： SCIE（2025版） ; ; CSCD（2025-2026年度） ; ; 科技核心（2024版）

摘要： In the mammalian genome, most CpGs are methylated. However, CpGs within the CpG islands (CGIs) are largely unmethylated, which are important for gene expression regulation. The mechanism underlying the low methylation levels at CGIs remains largely elusive. KDM2 proteins (KDM2A and KDM2B) are H3K36me2 demethylases known to bind specifically at CGIs. Here, we report that depletion of each or both KDM2 proteins, or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity, leads to an increase in DNA methylation at selective CGIs. The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b, indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs. In addition, the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment. Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner. Copyright (c) 2024, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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