QSER1 protects DNA methylation valleys from de novo methylation

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Abstract
Screen identifies demethylation regulator: DNA methylation was one of the first epigenetic mechanisms discovered, but there is a limited understanding of its regulation and dysregulation in the context of development and disease. Dixon et al. performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to identify DNA methylation regulators (see the Perspective by Gu and Goodell). A top screen hit, QSER1, proved to be essential for maintaining low methylation at DNA methylation valleys, which overlap with developmental genes and broad H3K27me3 and EZH2 peaks. Mechanistic examination revealed that QSER1 and the demethylating enzyme TET1 cooperate to safeguard developmental programs from de novo methylation by the enzyme DNMT3. Science , this issue p. eabd0875 ; see also p. 128
Funding Information
  • National Institutes of Health (R01 DK096239)
  • National Institutes of Health (R01 HG006827)
  • National Institutes of Health (P30CA008748)
  • Howard Hughes Medical Institute
  • American Diabetes Association (1-19-IBS-125)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK096239)

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