title: The nuclear envelope protein emerin binds directly to histone deacetylase 3 (HDAC3) and activates HDAC3 activity.
abstract: Organization of the genome is critical for maintaining cell-specific gene expression, ensuring proper cell function. It is well established that the nuclear lamina preferentially associates with repressed chromatin. However, the molecular mechanisms underlying repressive chromatin formation and maintenance at the nuclear lamina remain poorly understood. Here we show that emerin binds directly to HDAC3, the catalytic subunit of the nuclear co-repressor (NCoR) complex, and recruits HDAC3 to the nuclear periphery. Emerin binding stimulated the catalytic activity of HDAC3, and emerin-null cells exhibit increased H4K5 acetylation, which is the preferred target of the NCoR complex. Emerin-null cells exhibit an epigenetic signature similar to that seen in HDAC3-null cells. Emerin-null cells also had significantly less HDAC3 at the nuclear lamina. Collectively, these data support a model whereby emerin facilitates repressive chromatin formation at the nuclear periphery by increasing the catalytic activity of HDAC3.
authors.affiliation: Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Demmerle
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Koch
authors.forename: James M
authors.initials: JM
authors.lastname: Holaska
mesh_terms: D000818:Animals; D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004789:Enzyme Activation; D044127:Epigenesis, Genetic; D016678:Genome; D006655:Histone Deacetylases / Q000737:chemistry*; D006657:Histones / Q000737:chemistry; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D009136:Muscular Dystrophies / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry*; D011485:Protein Binding; D013347:Subcellular Fractions / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D002843:Chromatin; D006655:Histone Deacetylases; D006657:Histones; D008565:Membrane Proteins; D009687:Nuclear Proteins; D000099186:Histone Deacetylase 3; C092710:emerin