Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability (original) (raw)

1. Zhuqiang Zhang3,6,
2. Hui Wu4,6,
3. Yonghua Jiang2,
4. Lingjun Meng2,
5. Jun Xiong2,
6. Zuodong Zhao2,
7. Xiaohua Zhou2,
8. Jia Li2,
9. Hong Li2,
10. Yong Zheng2,
11. She Chen2,
12. Tao Cai2,
13. Shaorong Gao5 and
14. Bing Zhu2,3
15. 1College of Life Sciences, Beijing Normal University, Beijing 100875, China;
16. 2National Institute of Biological Sciences, Beijing 102206, China;
17. 3National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
18. 4National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin Province 130012, China;
19. 5School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
20. Corresponding authors: zhubing{at}ibp.ac.cn, topwuhui{at}jlu.edu.cn
21. ↵6 These authors contributed equally to this work.

Abstract

GLP and G9a are major H3K9 dimethylases and are essential for mouse early embryonic development. GLP and G9a both harbor ankyrin repeat domains that are capable of binding H3K9 methylation. However, the functional significance of their recognition of H3K9 methylation is unknown. Here, we report that the histone methyltransferase activities of GLP and G9a are stimulated by neighboring nucleosomes that are premethylated at H3K9. These stimulation events function in cis and are dependent on the H3K9 methylation binding activities of ankyrin repeat domains of GLP and G9a. Disruption of the H3K9 methylation-binding activity of GLP in mice causes growth retardation of embryos, ossification defects of calvaria, and postnatal lethality due to starvation of the pups. In mouse embryonic stem cells (ESCs) harboring a mutant GLP that lacks H3K9me1-binding activity, critical pluripotent genes, including Oct4 and Nanog, display inefficient establishment of H3K9me2 and delayed gene silencing during differentiation. Collectively, our study reveals a new activation mechanism for GLP and G9a that plays an important role in ESC differentiation and mouse viability.

• GLP
• G9a
• H3K9 methylation
• gene repression
• cell differentiation

Footnotes

• Supplemental material is available for this article.

• Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.254425.114.

• Received October 17, 2014.

• Accepted January 6, 2015.

• © 2015 Liu et al.; Published by Cold Spring Harbor Laboratory Press

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