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Volume 52 Issue 1
Jan.  2025
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Article Navigation >  Journal of Genetics and Genomics  > 2025  >  52(1): 39-50

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

doi: 10.1016/j.jgg.2024.10.012
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    a. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;

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    b. University of Chinese Academy of Sciences, Beijing 100049, China;

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    c. Department of Biochemistry & Molecular Biology, College of Natural Science, Michigan State University, East Lansing, MI 48824, USA;

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    d. State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

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We thank Dr. Xinyi Lu from Nankai University for the KDM2A antibody and Dr. Xudong Wu from Tianjin Medical University for the KDM2B antibody. This work was supported by the National Natural Science Foundation of China (32070607), the National Key Research and Development Program of China (2020YFA0804000), and the CAS Project for Young Scientists in Basic Research (YSBR-012).

  • Received Date: 2024-07-11
  • Accepted Date: 2024-10-31
  • Rev Recd Date: 2024-10-30
    • Available Online: 2025-07-11
  • Publish Date: 2024-11-08
    Abstract
  • 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.
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