Histone methyltransferase G9a contributes to H3K27 methylation in vivo

Wu, Hui; Chen, Xiuzhen; Xiong, Jun; Li, Yingfeng; Li, Hong; Ding, Xiaojun; Liu, Sheng; Chen, She; Gao, Shaorong; Zhu, Bing

doi:10.1038/cr.2010.157

Cited by 102 publications

(84 citation statements)

References 9 publications

(14 reference statements)

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“…1B, lane 3). This is most likely due to G9a's and GLP's in vitro catalytic activities at H3K27, as previously reported (Tachibana et al 2001;Wu et al 2011). Indeed, when residue Lys27 of H3 was mutated to alanine, the stimulation activity was observed at only the unmodified H3 histones but not the tagged premethylated H3 histones (Supplemental Fig.…”

Section: Resultssupporting

confidence: 56%

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

et al. 2015

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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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Section: Resultssupporting

confidence: 56%

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

et al. 2015

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“…These enzymes are implicated in a variety of disease and biological processes (6); they demonstrate both co-activator and co-repressor functions (6 -8) and interact with other SET domain-containing proteins including SETDB1, Suv39H1, and the PRC2 complex (9,10). G9a and GLP show similar substrate specificities (11-13); they methylate histones H1 (11,12,14), H3K27 (11,15) and H3K56 (16), as well as a number of non-histone proteins (17)(18)(19)(20)(21), but are best characterized as the major lysine methyltransferases involved in mono-and di-methylation of H3K9 (11,(22)(23)(24)(25).…”

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confidence: 99%

A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin

Simon

Parker

Liu

et al. 2015

Journal of Biological Chemistry

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Background: G9a-GLP lysine methyltransferases mono-and di-methylate histone H3 lysine 9 (H3K9me2). Results: Widely interspaced zinc finger (WIZ) regulates H3K9me2 levels through a mechanism that involves retention of G9a on chromatin. Conclusion:The G9a-GLP-WIZ complex has unique functions when bound to chromatin that are independent of the H3K9me2 mark. Significance: Combining pharmacologic and genetic manipulations is essential to any translational hypotheses related to G9a function.

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“…These enzymes work as heterodimers to introduce monomethyl and dimethyl modifications on histone H3 at Lys-9 [single-or dimethylated H3K9 (H3K9me1/me2] (7-10). In addition, several studies have shown that G9a and GLP mediate dimethylation of H3K27, both in vitro (11) and in vivo (12)(13)(14).…”

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Maintenance of gene silencing by the coordinate action of the H3K9 methyltransferase G9a/KMT1C and the H3K4 demethylase Jarid1a/KDM5A

Chaturvedi

Somasundaram

Singh

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Chromatin remodeling is essential for controlling the expression of genes during development. The histone-modifying enzyme G9a/KMT1C can act both as a coactivator and a corepressor of transcription. Here, we show that the dual function of G9a as a coactivator vs. a corepressor entails its association within two distinct protein complexes, one containing the coactivator Mediator and one containing the corepressor Jarid1a/KDM5A. Functionally, G9a is important in stabilizing the Mediator complex for gene activation, whereas its repressive function entails a coordinate action with the histone H3 lysine 4 (H3K4) demethylase Jarid1a for the maintenance of gene repression. The essential nature of cross-talk between the histone methyltransferase G9a and the demethylase Jarid1a is demonstrated on the embryonic E y -globin gene, where the concurrent introduction of repressive histone marks (dimethylated H3K9 and dimethylated H3K27) and removal of activating histone mark (trimethylated H3K4) is required for maintenance of gene silencing. Taken together with our previous demonstration of cross-talk between UTX and MLL2 to mediate activation of the adult β maj -globin gene, these data suggest a model where “active” and “repressive” cross-talk between histone-modifying enzymes coexist on the same multigene locus and play a crucial role in the precise control of developmentally regulated gene expression.

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Histone methyltransferase G9a contributes to H3K27 methylation in vivo

Cited by 102 publications

References 9 publications

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

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

A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin

Maintenance of gene silencing by the coordinate action of the H3K9 methyltransferase G9a/KMT1C and the H3K4 demethylase Jarid1a/KDM5A

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