QSER1 protects DNA methylation valleys from de novo methylation

Gary Dixon, Heng Pan, Dapeng Yang, Bess P. Rosen, Therande Jashari, Nipun Verma, Julian Pulecio, Inbal Caspi, Kihyun Lee, Stephanie Stransky, Abigail Glezer, Chang Liu, Marco Rivas, Ritu Kumar, Yahui Lan, Ingrid Torregroza, Chuan He, Simone Sidoli, Todd Evans, Olivier ElementoDanwei Huangfu

Research output: Contribution to journalArticlepeer-review

Abstract

DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition and removal of DNA methylation are known, but how they cooperate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to discover DNA methylation regulators. The top screen hit was an uncharacterized gene, QSER1, which proved to be a key guardian of bivalent promoters and poised enhancers of developmental genes, especially those residing in DNA methylation valleys (or canyons). We further demonstrate genetic and biochemical interactions of QSER1 and TET1, supporting their cooperation to safeguard transcriptional and developmental programs from DNMT3-mediated de novo methylation.

Original languageEnglish (US)
Article numbereabd0875
JournalScience
Volume372
Issue number6538
DOIs
StatePublished - Apr 9 2021

ASJC Scopus subject areas

  • General

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