title: Cross-talk between histone modifications in response to histone deacetylase inhibitors: MLL4 links histone H3 acetylation and histone H3K4 methylation.
abstract: Histones are subject to a wide variety of post-translational modifications that play a central role in gene activation and silencing. We have used histone modification-specific antibodies to demonstrate that two histone modifications involved in gene activation, histone H3 acetylation and H3 lysine 4 methylation, are functionally linked. This interaction, in which the extent of histone H3 acetylation determines both the abundance and the "degree" of H3K4 methylation, plays a major role in the epigenetic response to histone deacetylase inhibitors. A combination of in vivo knockdown experiments and in vitro methyltransferase assays shows that the abundance of H3K4 methylation is regulated by the activities of two opposing enzyme activities, the methyltransferase MLL4, which is stimulated by acetylated substrates, and a novel and as yet unidentified H3K4me3 demethylase.
authors.affiliation: Chromatin and Gene Expression Group, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom and.
authors.forename: Karl P
authors.initials: KP
authors.lastname: Nightingale
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Susanne
authors.initials: S
authors.lastname: Gendreizig
authors.affiliation: Chromatin and Gene Expression Group, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom and.
authors.forename: Darren A
authors.initials: DA
authors.lastname: White
authors.affiliation: Chromatin and Gene Expression Group, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom and.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bradbury
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
authors.forename: Florian
authors.initials: F
authors.lastname: Hollfelder
authors.affiliation: Chromatin and Gene Expression Group, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom and. Electronic address: b.m.turner@bham.ac.uk.
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Turner
mesh_terms: D000107:Acetylation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects* / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; D006655:Histone Deacetylases