QSER1 protects DNA methylation valleys from de novo methylation Journal Article
| Authors: | Dixon, G.; Pan, H.; Yang, D.; Rosen, B. P.; 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. |
| Article Title: | QSER1 protects DNA methylation valleys from de novo methylation |
| 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. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
| Keywords: | human cell; promoter region; dna methylation; enhancer region; developmental gene; article; crispr-cas9 system; human embryonic stem cell |
| Journal Title: | Science |
| Volume: | 372 |
| Issue: | 6538 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2021-04-09 |
| Start Page: | eabd0875 |
| Language: | English |
| DOI: | 10.1126/science.abd0875 |
| PUBMED: | 33833093 |
| PROVIDER: | scopus |
| PMCID: | PMC8185639 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 May 2021 -- Source: Scopus |
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