title: Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription.
abstract: Regulation of gene activity is mediated by alterations in chromatin organization. In addition, chromatin organization may be governed in part by interactions with structural components of the nucleus. The nuclear lamins comprise the lamina and a variety of nucleoplasmic assemblies that together are major structural components of the nucleus. Furthermore, lamins and lamin-associated proteins have been reported to bind chromatin. These observations suggest that the nuclear lamins may be involved in the regulation of gene activity. In this report, we test this possibility by disrupting the normal organization of nuclear lamins with a dominant negative lamin mutant lacking the NH2-terminal domain. We find that this disruption inhibits RNA polymerase II activity in both mammalian cells and transcriptionally active embryonic nuclei from Xenopus laevis. The inhibition appears to be specific for polymerase II as disruption of lamin organization does not detectably inhibit RNA polymerases I and III. Furthermore, immunofluorescence observations indicate that this selective inhibition of polymerase II-dependent transcription involves the TATA binding protein, a component of the basal transcription factor TFIID.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Spann
authors.forename: Anne E
authors.initials: AE
authors.lastname: Goldman
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Sui
authors.initials: S
authors.lastname: Huang
authors.forename: Robert D
authors.initials: RD
authors.lastname: Goldman
mesh_terms: D016475:3T3 Cells; D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D006367:HeLa Cells; D006801:Humans; D034882:Lamins; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic; D014982:Xenopus laevis
chemical_list: D000546:Amanitins; D034882:Lamins; D009687:Nuclear Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D012319:RNA Polymerase II