title: Histone deacetylase interacts directly with DNA topoisomerase II.
abstract: Histone deacetylases (HDACs) modify nucleosomal histones, have a key role in the regulation of gene transcription, and may be involved in cell-cycle regulation, differentiation and human cancer. Purified recombinant human HDAC1 protein was used to screen a cDNA expression library, and one of the clones identified encoded DNA topoisomerase II (Topo II), an enzyme known to have a role in transcriptional regulation and chromatin organization. Coimmunoprecipitation experiments indicate that HDAC1 and HDAC2 are associated with Topo II in vivo under normal physiological conditions. Complexes containing Topo II possess HDAC activities, and complexes containing HDAC1 or HDAC2 possess Topo II activities. HDAC and Topo II modify each other's activity in vitro and in vivo. Our results indicate the existence of a functionally coupled complex between these two enzymes and offer insights into the potential mechanisms of action of both enzymes.
authors.affiliation: H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, Florida, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Tsai
authors.forename: N
authors.initials: N
authors.lastname: Valkov
authors.forename: W M
authors.initials: WM
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Gump
authors.forename: D
authors.initials: D
authors.lastname: Sullivan
authors.forename: E
authors.initials: E
authors.lastname: Seto
mesh_terms: D000107:Acetylation; D002384:Catalysis; D002843:Chromatin / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D006609:High Mobility Group Proteins / Q000032:analysis; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins
chemical_list: D002843:Chromatin; D018076:DNA, Complementary; D006609:High Mobility Group Proteins; D046911:Macromolecular Substances; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D004250:DNA Topoisomerases, Type II