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

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...

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Autores principales: Liu, Nan, Zhang, Zhuqiang, Wu, Hui, Jiang, Yonghua, Meng, Lingjun, Xiong, Jun, Zhao, Zuodong, Zhou, Xiaohua, Li, Jia, Li, Hong, Zheng, Yong, Chen, She, Cai, Tao, Gao, Shaorong, Zhu, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335294/
https://www.ncbi.nlm.nih.gov/pubmed/25637356
http://dx.doi.org/10.1101/gad.254425.114
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author Liu, Nan
Zhang, Zhuqiang
Wu, Hui
Jiang, Yonghua
Meng, Lingjun
Xiong, Jun
Zhao, Zuodong
Zhou, Xiaohua
Li, Jia
Li, Hong
Zheng, Yong
Chen, She
Cai, Tao
Gao, Shaorong
Zhu, Bing
author_facet Liu, Nan
Zhang, Zhuqiang
Wu, Hui
Jiang, Yonghua
Meng, Lingjun
Xiong, Jun
Zhao, Zuodong
Zhou, Xiaohua
Li, Jia
Li, Hong
Zheng, Yong
Chen, She
Cai, Tao
Gao, Shaorong
Zhu, Bing
author_sort Liu, Nan
collection PubMed
description 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.
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spelling pubmed-43352942015-08-15 Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability Liu, Nan Zhang, Zhuqiang Wu, Hui Jiang, Yonghua Meng, Lingjun Xiong, Jun Zhao, Zuodong Zhou, Xiaohua Li, Jia Li, Hong Zheng, Yong Chen, She Cai, Tao Gao, Shaorong Zhu, Bing Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2015-02-15 /pmc/articles/PMC4335294/ /pubmed/25637356 http://dx.doi.org/10.1101/gad.254425.114 Text en © 2015 Liu et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Liu, Nan
Zhang, Zhuqiang
Wu, Hui
Jiang, Yonghua
Meng, Lingjun
Xiong, Jun
Zhao, Zuodong
Zhou, Xiaohua
Li, Jia
Li, Hong
Zheng, Yong
Chen, She
Cai, Tao
Gao, Shaorong
Zhu, Bing
Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability
title Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability
title_full Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability
title_fullStr Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability
title_full_unstemmed Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability
title_short Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability
title_sort recognition of h3k9 methylation by glp is required for efficient establishment of h3k9 methylation, rapid target gene repression, and mouse viability
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335294/
https://www.ncbi.nlm.nih.gov/pubmed/25637356
http://dx.doi.org/10.1101/gad.254425.114
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