QSER1 protects DNA methylation valleys from de novo methylation-Reference-Cited by-同舟云学术

QSER1 protects DNA methylation valleys from de novo methylation

Published:2021-04-09 Issue:6538 Volume:372 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Dixon Gary¹²^ORCID,Pan Heng³^ORCID,Yang Dapeng²,Rosen Bess P.¹²^ORCID,Jashari Therande¹²^ORCID,Verma Nipun²⁴,Pulecio Julian²^ORCID,Caspi Inbal¹²^ORCID,Lee Kihyun²^ORCID,Stransky Stephanie⁵^ORCID,Glezer Abigail²^ORCID,Liu Chang⁶⁷^ORCID,Rivas Marco⁶⁷^ORCID,Kumar Ritu⁸^ORCID,Lan Yahui⁸,Torregroza Ingrid⁸^ORCID,He Chuan⁶⁷^ORCID,Sidoli Simone⁵^ORCID,Evans Todd⁸,Elemento Olivier³^ORCID,Huangfu Danwei²^ORCID

Affiliation:

1. Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.

2. Developmental Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.

3. Department of Physiology and Biophysics, Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.

4. Weill Graduate School of Medical Sciences at Cornell University–The Rockefeller University–Sloan Kettering Institute Tri-Institutional M.D.-Ph.D. Program, New York, NY 10065, USA.

5. Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

6. Department of Chemistry, Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.

7. Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.

8. Department of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.

Abstract

Screen identifies demethylation regulator DNA methylation was one of the first epigenetic mechanisms discovered, but there is a limited understanding of its regulation and dysregulation in the context of development and disease. Dixon et al. performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to identify DNA methylation regulators (see the Perspective by Gu and Goodell). A top screen hit, QSER1, proved to be essential for maintaining low methylation at DNA methylation valleys, which overlap with developmental genes and broad H3K27me3 and EZH2 peaks. Mechanistic examination revealed that QSER1 and the demethylating enzyme TET1 cooperate to safeguard developmental programs from de novo methylation by the enzyme DNMT3. Science , this issue p. eabd0875 ; see also p. 128

Funder

National Institutes of Health

Howard Hughes Medical Institute

American Diabetes Association

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference71 articles.

1. EUKARYOTIC CYTOSINE METHYLTRANSFERASES

2. DNA methylation: roles in mammalian development