title: Role of histone deacetylases in gene regulation at nuclear lamina.
abstract: Theoretical models suggest that gene silencing at the nuclear periphery may involve "closing" of chromatin by transcriptional repressors, such as histone deacetylases (HDACs). Here we provide experimental evidence confirming these predictions. Histone acetylation, chromatin compactness, and gene repression in lamina-interacting multigenic chromatin domains were analyzed in Drosophila S2 cells in which B-type lamin, diverse HDACs, and lamina-associated proteins were downregulated by dsRNA. Lamin depletion resulted in decreased compactness of the repressed multigenic domain associated with its detachment from the lamina and enhanced histone acetylation. Our data reveal the major role for HDAC1 in mediating deacetylation, chromatin compaction, and gene silencing in the multigenic domain, and an auxiliary role for HDAC3 that is required for retention of the domain at the lamina. These findings demonstrate the manifold and central involvement of class I HDACs in regulation of lamina-associated genes, illuminating a mechanism by which these enzymes can orchestrate normal and pathological development.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Beatrice C
authors.initials: BC
authors.lastname: Milon
authors.forename: Haibo
authors.initials: H
authors.lastname: Cheng
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Tselebrovsky
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Lavrov
authors.forename: Valentina V
authors.initials: VV
authors.lastname: Nenasheva
authors.forename: Elena A
authors.initials: EA
authors.lastname: Mikhaleva
authors.forename: Yuri Y
authors.initials: YY
authors.lastname: Shevelyov
authors.forename: Dmitry I
authors.initials: DI
authors.lastname: Nurminsky
mesh_terms: D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002843:Chromatin / Q000201:enzymology / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D034921:Lamin Type B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D034881:Nuclear Lamina / Q000201:enzymology / Q000235:genetics*; D012330:RNA, Double-Stranded / Q000235:genetics; D014158:Transcription, Genetic; D000099186:Histone Deacetylase 3
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D006657:Histones; D034921:Lamin Type B; D012330:RNA, Double-Stranded; D000099186:Histone Deacetylase 3; C512966:HDAC1 protein, Drosophila