title: G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells.
abstract: DNA methylation at imprinting control regions (ICRs) is established in gametes in a sex-specific manner and has to be stably maintained during development and in somatic cells to ensure the correct monoallelic expression of imprinted genes. In addition to DNA methylation, the ICRs are marked by allele-specific histone modifications. Whether these marks are essential for maintenance of genomic imprinting is largely unclear. Here, we show that the histone H3 lysine 9 methylases G9a and GLP are required for stable maintenance of imprinted DNA methylation in embryonic stem cells; however, their catalytic activity and the G9a/GLP-dependent H3K9me2 mark are completely dispensable for imprinting maintenance despite the genome-wide loss of non-imprinted DNA methylation in H3K9me2-depleted cells. We provide additional evidence that the G9a/GLP complex protects imprinted DNA methylation by recruitment of de novo DNA methyltransferases, which antagonize TET dioxygenass-dependent erosion of DNA methylation at ICRs.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Tuo
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Ausma
authors.initials: A
authors.lastname: Termanis
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Burak
authors.initials: B
authors.lastname: Özkan
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Xun X
authors.initials: XX
authors.lastname: Bao
authors.affiliation: Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Jayne
authors.initials: J
authors.lastname: Culley
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Flavia
authors.initials: F
authors.lastname: de Lima Alves
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK; Department of Bioanalytics, Institute of Biotechnology, Technische Universität Berlin, 10623 Berlin, Germany.
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.affiliation: Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ramsahoye
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK. Electronic address: istancheva@ed.ac.uk.
authors.forename: Irina
authors.initials: I
authors.lastname: Stancheva
mesh_terms: D002460:Cell Line; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018392:Genomic Imprinting; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans
chemical_list: D006649:Histocompatibility Antigens; C455847:EHMT1 protein, human; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase