| Literature DB >> 33833093 |
Gary Dixon1,2, Heng Pan3, Dapeng Yang2, Bess P Rosen1,2, Therande Jashari1,2, Nipun Verma2,4, Julian Pulecio2, Inbal Caspi1,2, Kihyun Lee2, Stephanie Stransky5, Abigail Glezer2, Chang Liu6,7, Marco Rivas6,7, Ritu Kumar8, Yahui Lan8, Ingrid Torregroza8, Chuan He6,7, Simone Sidoli5, Todd Evans8, Olivier Elemento9, Danwei Huangfu10.
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.Entities:
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Year: 2021 PMID： 33833093 PMCID： PMC8185639 DOI： 10.1126/science.abd0875
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728