ArticleThe Journal of biological chemistry2021
Heterodimerization of H3K9 histone methyltransferases G9a and GLP activates methyl reading and writing capabilities.
Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Deep phenotyping of EHMT1 ankyrin repeat domain missense variants in Kleefstra syndrome by multi-tiered structural genomics analyses at atomic resolution.Human molecular genetics · 2026Article
- De novo EHMT2 variants cause an autosomal dominant EHMT2-related Kleefstra syndrome via loss of G9a methyltransferase activity.Nature communications · 2026Article
- Histone 3 lysine 9 dimethylation by the G9a-GLP heterodimer requires intranucleosomal product reading.bioRxiv : the preprint server for biology · 2026Article
- A role forFrontiers in genetics · 2026Article
- A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Maturation and persistence of CAR T cells derived from human pluripotent stem cells via chemical inhibition of G9a/GLP.Cell stem cell · 2025Article
- EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell-Dependent Manner.Molecular cancer research : MCR · 2024Article
- Distinct H3K9me3 heterochromatin maintenance dynamics govern different gene programmes and repeats in pluripotent cells.Nature cell biology · 2024Article
- A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.PLoS biology · 2024Article
- Distinct H3K9me3 heterochromatin maintenance dynamics govern different gene programs and repeats in pluripotent cells.bioRxiv : the preprint server for biology · 2024Article
- Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.Molecular cancer therapeutics · 2024Article
- Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.American journal of human genetics · 2024Article
- Histone Methyltransferases G9a/International journal of molecular sciences · 2023Article
- Distinct functions of EHMT1 and EHMT2 in cancer chemotherapy and immunotherapy.bioRxiv : the preprint server for biology · 2023Article
- Intrinsic catalytic properties of histone H3 lysine-9 methyltransferases preserve monomethylation levels under low S-adenosylmethionine.The Journal of biological chemistry · 2023Article
- A multi-layered computational structural genomics approach enhances domain-specific interpretation of Kleefstra syndrome variants in EHMT1.Computational and structural biotechnology journal · 2023Article
- Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants.The Journal of biological chemistry · 2022Article
- Targets of histone H3 lysine 9 methyltransferases.Frontiers in cell and developmental biology · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Unique among metazoan repressive histone methyltransferases, G9a and GLP, which chiefly target histone 3 lysine 9 (H3K9), require dimerization for productive H3K9 mono (me1)- and dimethylation (me2) in vivo. Intriguingly, even though each enzyme can independently methylate H3K9, the predominant active form in vivo is a heterodimer of G9a and GLP. How dimerization influences the central H3K9 methyl binding ("reading") and deposition ("writing") activity of G9a and GLP and why heterodimerization is essential in vivo remains opaque. Here, we examine the H3K9me "reading" and "writing" activities of defined, recombinantly produced homo- and heterodimers of G9a and GLP. We find that both reading and writing are significantly enhanced in the heterodimer. Compared with the homodimers, the heterodimer has higher recognition of H3K9me2, and a striking ∼10-fold increased turnover rate for nucleosomal substrates under multiple turnover conditions, which is not evident on histone tail peptide substrates. Cross-linking Mass Spectrometry suggests that differences between the homodimers and the unique activity of the heterodimer may be encoded in altered ground state conformations, as each dimer displays different domain contacts. Our results indicate that heterodimerization may be required to relieve autoinhibition of H3K9me reading and chromatin methylation evident in G9a and GLP homodimers. Relieving this inhibition may be particularly important in early differentiation when large tracts of H3K9me2 are typically deposited by G9a-GLP, which may require a more active form of the enzyme.
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