QSER1 protects DNA methylation valleys from de novo methylation. Academic Article uri icon

Overview

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.

publication date

  • April 9, 2021

Research

keywords

  • DNA
  • DNA Methylation
  • Human Embryonic Stem Cells

Identity

PubMed Central ID

  • PMC8185639

Scopus Document Identifier

  • 85104166307

Digital Object Identifier (DOI)

  • 10.1126/science.abd0875

PubMed ID

  • 33833093

Additional Document Info

volume

  • 372

issue

  • 6538