QSER1 protects DNA methylation valleys from de novo methylation.

TitleQSER1 protects DNA methylation valleys from de novo methylation.
Publication TypeJournal Article
Year of Publication2021
AuthorsDixon G, Pan H, Yang D, Rosen BP, Jashari T, Verma N, Pulecio J, Caspi I, Lee K, Stransky S, Glezer A, Liu C, Rivas M, Kumar R, Lan Y, Torregroza I, He C, Sidoli S, Evans T, Elemento O, Huangfu D
Date Published2021 04 09
KeywordsCRISPR-Cas Systems, DNA, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Gene Knock-In Techniques, Gene Knockout Techniques, Genome, Human, Human Embryonic Stem Cells, Humans, Mixed Function Oxygenases, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins, Transcription, Genetic

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, , 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.

Alternate JournalScience
PubMed ID33833093
PubMed Central IDPMC8185639
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
T32 GM008539 / GM / NIGMS NIH HHS / United States
T32 HD060600 / HD / NICHD NIH HHS / United States
R01 HG006827 / HG / NHGRI NIH HHS / United States
R01 DK096239 / DK / NIDDK NIH HHS / United States