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

doi:10.1101/gad.254425.114

Cited by 100 publications

(106 citation statements)

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“…When the Ehmt1 Ank repeat domains are inactivated by mutation, the Ehmt1/2 complex is no longer able to bind effectively to monomethylated H3K9. 24 However, when the SET domain of Ehmt1 is inactivated by mutation embryos are viable and survive to adulthood, 25 in contrast to Ehmt2 SET mutations, which are embryonic lethal. 26 This data implies that Ehmt1 plays a particularly important role in recruiting the complex to monomethylated sites, whereas Ehmt2 is required for the methyltransferase activity.…”

Section: The Ehmt1/2 Complexmentioning

confidence: 99%

The expanding role of the Ehmt2/G9a complex in neurodevelopment

2017

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Epigenetic regulators play a crucial role in neurodevelopment. One such epigenetic complex, Ehmt1/2 (G9a/GLP), is essential for repressing gene transcription by methylating H3K9 in a highly tissue-and temporal-specific manner. Recently, data has emerged suggesting that this complex plays additional roles in regulating the activity of numerous other non-histone proteins. While much is known about the downstream effects of Ehmt1/2 function, evidence is only beginning to come to light suggesting the control of Ehmt1/2 function may be, at least in part, due to context-dependent binding partners. Here we review emerging roles for the Ehmt1/2 complex suggesting that it may play a much larger role than previously recognized, and discuss binding partners that we and others have recently characterized which act to coordinate its activity during early neurodevelopment.

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Section: The Ehmt1/2 Complexmentioning

confidence: 99%

The expanding role of the Ehmt2/G9a complex in neurodevelopment

2017

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“…5G). To extend these findings, we analyzed ChIP-seq profiles of H3K9me1/2 in ESCs (Liu et al 2015) and also performed H3K9me2 ChIP-seq in E8.5 embryos. According to the ChIP-seq data, HMRs are marked by H3K9 mono-and dimethylation in ESCs and E8.5 embryos, but the enrichment for these marks is only slightly higher than that of the surrounding sequences (Fig.…”

Section: Interplay Between H3k9me2 and Dna Methylation In Embryosmentioning

confidence: 99%

“…GSE46545) (Mozzetta et al 2014), H3K9me1/2 in ESCs (GEO accession no. GSE54412) (Liu et al 2015), H3K4me2 in ESCs (GEO accession no. GSE30203) (Stadler et al 2011), and H3K9me2 in E8.5 embryos (this study).…”

Section: Data Analysis and Characterization Of Hmrsmentioning

confidence: 99%

EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos

et al. 2015

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The extent to which histone modifying enzymes contribute to DNA methylation in mammals remains unclear. Previous studies suggested a link between the lysine methyltransferase EHMT2 (also known as G9A and KMT1C) and DNA methylation in the mouse. Here, we used a model of knockout mice to explore the role of EHMT2 in DNA methylation during mouse embryogenesis. The Ehmt2 gene is expressed in epiblast cells but is dispensable for global DNA methylation in embryogenesis. In contrast, EHMT2 regulates DNA methylation at specific sequences that include CpG-rich promoters of germline-specific genes. These loci are bound by EHMT2 in embryonic cells, are marked by H3K9 dimethylation, and have strongly reduced DNA methylation in Ehmt2 −/− embryos. EHMT2 also plays a role in the maintenance of germline-derived DNA methylation at one imprinted locus, the Slc38a4 gene. Finally, we show that DNA methylation is instrumental for EHMT2-mediated gene silencing in embryogenesis. Our findings identify EHMT2 as a critical factor that facilitates repressive DNA methylation at specific genomic loci during mammalian development.

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“…Interestingly, these ankyrin domains were shown to possess a methyl-Lysbinding module that allows binding to H3K9me1 and H3K9me2 marks, independently of SET domains 14 . Binding to H3K9me2 by GLP through its ankyrin domains stimulates its activity on the neighbouring nucleosomes and is required for the establishment of H3K9 methylation in vivo 15 .…”

mentioning

confidence: 99%

Sound of silence: the properties and functions of repressive Lys methyltransferases

Mozzetta¹,

Boyarchuk²,

Pontis³

et al. 2015

Nat Rev Mol Cell Biol

162

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The methylation of histone Lys residues by Lys methyltransferases (KMTs) regulates chromatin organization and either activates or represses gene expression, depending on the residue that is targeted. KMTs are emerging as key components in several cellular processes, and their deregulation is often associated with pathogenesis. Here, we review the current knowledge on the main KMTs that are associated with gene silencing: namely, those responsible for methylating histone H3 Lys 9 (H3K9), H3K27 and H4K20. We discuss their biochemical properties and the various mechanisms by which they are targeted to the chromatin and regulate gene expression, as well as new data on the interplay between them and other chromatin modifiers.

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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

Cited by 100 publications

References 50 publications

The expanding role of the Ehmt2/G9a complex in neurodevelopment

The expanding role of the Ehmt2/G9a complex in neurodevelopment

EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos

Sound of silence: the properties and functions of repressive Lys methyltransferases

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