ArticleEpigenetics & chromatin2018
Tri-methylation of ATF7IP by G9a/GLP recruits the chromodomain protein MPP8.
Article in Epigenetics & chromatin, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
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- Replicon-based genome-wide CRISPR knockout screening for the identification of host factors involved in viral replication.Nature communications · 2025Article
- Structure and Methyl-lysine Binding Selectivity of the HUSH Complex Subunit MPP8.Journal of molecular biology · 2025Article
- RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex.Nucleic acids research · 2025Article
- Determining the Substrate Specificity of Lysine Methyltransferases.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Emergent properties of the lysine methylome reveal regulatory roles via protein interactions and histone mimicry.Epigenomics · 2025Article
- A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.PLoS biology · 2024Article
- Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.American journal of human genetics · 2024Article
- Keep quiet: the HUSH complex in transcriptional silencing and disease.Nature structural & molecular biology · 2024Review
- Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation.Cell chemical biology · 2023Article
- Regulation of the heterochromatin spreading reaction byOpen biology · 2023Review
- Writers and readers of H3K9me2 form distinct protein networks during the cell cycle that include candidates for H3K9 mimicry.Bioscience reports · 2023Article
- Activity Guided Azide-methyllysine Photo-trapping for Substrate Profiling of Lysine Demethylases.Journal of the American Chemical Society · 2023Article
- Co-transcriptional genome surveillance by HUSH is coupled to termination machinery.Molecular cell · 2023Article
- RNA-mediated heterochromatin formation at repetitive elements in mammals.The EMBO journal · 2023Review
- A specific G9a inhibitor unveils BGLT3 lncRNA as a universal mediator of chemically induced fetal globin gene expression.Nature communications · 2023Article
- Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance.Nature reviews. Molecular cell biology · 2022Review
- Discovery of the First-in-Class G9a/GLP Covalent Inhibitors.Journal of medicinal chemistry · 2022Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundG9a and the related enzyme GLP were originally identified as histone lysine methyltransferases and then shown to also methylate several other non-histone proteins.
resultsHere, we performed a comprehensive screen to identify their substrates in mouse embryonic stem cells (mESCs). We identified 59 proteins, including histones and other known substrates. One of the identified substrates, activating transcriptional factor 7-interacting protein 1 (ATF7IP), is tri-methylated at a histone H3 lysine 9 (H3K9)-like mimic by the G9a/GLP complex, although this complex mainly introduces di-methylation on H3K9 and DNA ligase 1 (LIG1) K126 in cells. The catalytic domain of G9a showed a higher affinity for di-methylated lysine on ATF7IP than LIG1, which may create different methylation levels of different substrates in cells. Furthermore, we found that M-phase phosphoprotein 8 (MPP8), known as a H3K9me3-binding protein, recognizes methylated ATF7IP via its chromodomain. MPP8 is also a known component of the human silencing hub complex that mediates silencing of transgenes via SETDB1 recruitment, which is a binding partner of ATF7IP. Although the interaction between ATF7IP and SETDB1 does not depend on ATF7IP methylation, we found that induction of SETDB1/MPP8-mediated reporter-provirus silencing is delayed in mESCs expressing only an un-methylatable mutant of ATF7IP.
conclusionsOur findings provide new insights into the roles of lysine methylation in non-histone substrates which are targeted by the G9a/GLP complex and suggest a potential function of ATF7IP methylation in SETDB1/MPP8-mediated transgene silencing.
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