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Research Paper

SETD6 monomethylates H2AZ on lysine 7 and is required for the maintenance of embryonic stem cell self-renewal

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Pages 177-183 | Received 19 Dec 2012, Accepted 26 Dec 2012, Published online: 16 Jan 2013
 

Abstract

The histone H2A variant H2AZ is an essential chromatin signaling factor. Herein, we report that H2AZ is monomethylated at lysine 7 (H2AZK7me1) by the lysine methyltransferase SETD6. We observed that methylation of H2AZ increased noticeably upon cellular differentiation of mouse embryonic stem cells (mESCs). H2AZK7me1 and the repressive H3K27me3 mark were found near the transcriptional start sites of differentiation marker genes, but were removed upon retinoic acid-induced cellular differentiation. The depletion of Setd6 in mESCs led to cellular differentiation, compromised self-renewal, and poor clonogenicity. These findings demonstrate that mESCs require Setd6 for self-renewal and portray H2AZK7me1 as a marker of cellular differentiation.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The library screen was initiated in the laboratory of Or Gozani at Stanford University. This work was supported by Canadian Institute of Health Research (CIHR) grants (MOP-93811 and MOP-67070) and Weekend to End Women's Cancers grant from the Jewish General Hospital to SR, National Science Foundation (CBET-0941143) and a National Institutes of Health (NIH) grants (DP2OD007447) to BAG, and NIH (5R01GM078465) grant to IRL. O.B. held a postdoctoral fellowship from the CIHR and was supported by the McGill Integrated Cancer Research Training Program (FRN53888) while at McGill University. O.B. is supported by the Newcastle’s Biomedical Fellowship Programme, which is in part funded by the Wellcome Trust’s Institutional Strategic Support Fund.

Supplemental Materials

Supplemental materials may be found here: www.landesbioscience.com/journals/epigenetics/article/23416