title: The nuclear-envelope protein and transcriptional repressor LAP2beta interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation.
abstract: Nuclear-envelope proteins have been implicated in diverse and fundamental cell functions, among them transcriptional regulation. Gene expression at the territory of the nuclear periphery is known to be repressed by epigenetic modifications such as histone deacetylation and methylation. However, the mechanism by which nuclear-envelope proteins are involved in such modifications is still obscure. We have previously shown that LAP2beta, an integral nuclear-envelope protein that contains the chromatin-binding LEM domain, was able to repress the transcriptional activity of the E2F5-DP3 heterodimer. Here, we show that LAP2beta's repressive activity is more general, encompassing various E2F members as well as other transcription factors such as p53 and NF-kappaB. We further show that LAP2beta interacts at the nuclear envelope with HDAC3, a class-I histone deacetylase, and that TSA (an HDAC inhibitor) abrogates LAP2beta's repressive activity. Finally, we show that LAP2beta is capable of inducing histone-H4 deacetylation. Our data provide evidence for the existence of a previously unknown repressive complex, composed of an integral nuclear membrane protein and a histone modifier, at the nuclear periphery.
authors.affiliation: Sheba Cancer Research Center and Institute of Hematology, The Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Somech
authors.forename: Sigal
authors.initials: S
authors.lastname: Shaklai
authors.forename: Orit
authors.initials: O
authors.lastname: Geller
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Amos J
authors.initials: AJ
authors.lastname: Simon
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Einav Nili
authors.initials: EN
authors.lastname: Gal-Yam
mesh_terms: D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000099186:Histone Deacetylase 3
chemical_list: D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D006877:Hydroxamic Acids; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000099186:Histone Deacetylase 3; C093413:lamina-associated polypeptide 2; C012589:trichostatin A