title: Genes are often sheltered from the global histone hyperacetylation induced by HDAC inhibitors.
abstract: Histone deacetylase inhibitors (HDACi) are increasingly used as therapeutic agents, but the mechanisms by which they alter cell behaviour remain unclear. Here we use microarray expression analysis to show that only a small proportion of genes (∼9%) have altered transcript levels after treating HL60 cells with different HDACi (valproic acid, Trichostatin A, suberoylanilide hydroxamic acid). Different gene populations respond to each inhibitor, with as many genes down- as up-regulated. Surprisingly, HDACi rarely induced increased histone acetylation at gene promoters, with most genes examined showing minimal change, irrespective of whether genes were up- or down-regulated. Many genes seem to be sheltered from the global histone hyperacetyation induced by HDACi.
authors.affiliation: Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Halsall
authors.forename: Vibhor
authors.initials: V
authors.lastname: Gupta
authors.forename: Laura P
authors.initials: LP
authors.lastname: O'Neill
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Turner
authors.forename: Karl P
authors.initials: KP
authors.lastname: Nightingale
mesh_terms: D000107:Acetylation / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077337:Vorinostat; D014635:Valproic Acid