biostudies-literatureVinson DANIH NIGMSNIGMS NIH HHS36https://www.ebi.ac.uk/biostudies/studies/S-EPMC9677696biostudies-literatureUnknown15(1)Epigenetic modifications to histone proteins serve an important role in regulating permissive and repressive chromatin states, but despite the identification of many histone PTMs and their perceived role, the epigenetic writers responsible for generating these chromatin signatures are not fully characterized. Here, we report that the canonical histone H3K9 methyltransferases EHMT1/GLP and EHMT2/G9a are capable of catalyzing methylation of histone H3 lysine 23 (H3K23). Our data show that while both enzymes can mono- and di-methylate H3K23, only EHMT1/GLP can tri-methylate H3K23. We also show that pharmacologic inhibition or genetic ablation of EHMT1/GLP and/or EHMT2/G9a leads to decreased H3K23 methylation in mammalian cells. Taken together, this work identifies H3K23 as a new direct methylEpigenetics & chromatinDe novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.PMC9677696F31GM130114-03F31 GM130114R01 GM118760R01GM118760Taverna SDVinson DAO'Meally RNStephens KEBhat SCole RNDancy BCRYegnasubramanian SfalseDe novo methylation of histone H3K23 by the methyltransferases EHMT1/GLP and EHMT2/G9a.Epigenetic modifications to histone proteins serve an important role in regulating permissive and repressive chromatin states, but despite the identification of many histone PTMs and their perceived role, the epigenetic writers responsible for generating these chromatin signatures are not fully characterized. Here, we report that the canonical histone H3K9 methyltransferases EHMT1/GLP and EHMT2/G9a are capable of catalyzing methylation of histone H3 lysine 23 (H3K23). Our data show that while both enzymes can mono- and di-methylate H3K23, only EHMT1/GLP can tri-methylate H3K23. We also show that pharmacologic inhibition or genetic ablation of EHMT1/GLP and/or EHMT2/G9a leads to decreased H3K23 methylation in mammalian cells. Taken together, this work identifies H3K23 as a new direct methyl2022-01-01T00:00:00Z2022 Nov2025-04-18T22:30:33.212Z2025-02-19T04:38:06.971ZS-EPMC96776963641149110.1186/s13072-022-00468-1