title: A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase.
abstract: Chromatin structure plays a crucial regulatory role in the control of gene expression. In eukaryotic nuclei, enzymatic complexes can alter this structure by both targeted covalent modification and ATP-dependent chromatin remodeling. Modification of histone amino termini by acetyltransferases and deacetylases correlates with transcriptional activation and repression [1-3], cell growth [4], and tumorigenesis [5]. Chromatin-remodeling enzymes of the Snf2 superfamily use ATP hydrolysis to restructure nucleosomes and chromatin, events which correlate with activation of transcription [6,7]. We purified a multi-subunit complex from Xenopus laevis eggs which contains six putative subunits including the known deacetylase subunits Rpd3 and RbAp48/p46 [8] as well as substoichiometric quantities of the deacetylase-associated protein Sin3 [9-13]. In addition, we identified one of the other components of the complex to be Mi-2, a Snf2 superfamily member previously identified as an autoantigen in the human connective tissue disease dermatomyositis [14,15]. We found that nucleosome-stimulated ATPase activity precisely copurified with both histone deacetylase activity and the deacetylase enzyme complex. This association of a histone deacetylase with a Snf2 superfamily ATPase suggests a functional link between these two disparate classes of chromatin regulators.
authors.affiliation: Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Wade
authors.forename: P L
authors.initials: PL
authors.lastname: Jones
authors.forename: D
authors.initials: D
authors.lastname: Vermaak
authors.forename: A P
authors.initials: AP
authors.lastname: Wolffe
mesh_terms: D000251:Adenosine Triphosphatases / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D004265:DNA Helicases; D003882:Dermatomyositis / Q000201:enzymology / Q000276:immunology; D005260:Female; D006655:Histone Deacetylases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D009865:Oocytes / Q000737:chemistry / Q000201:enzymology*; D014982:Xenopus laevis
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D046911:Macromolecular Substances; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; D004265:DNA Helicases