RTegulation 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.
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18 February 2002
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February 18 2002
Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription
Timothy P. Spann,
Timothy P. Spann
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
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Anne E. Goldman,
Anne E. Goldman
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
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Chen Wang,
Chen Wang
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
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Sui Huang,
Sui Huang
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
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Robert D. Goldman
Robert D. Goldman
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
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Timothy P. Spann
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
Anne E. Goldman
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
Chen Wang
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
Sui Huang
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
Robert D. Goldman
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, IL 60611
Address correspondence to Robert D. Goldman, Department of Cell and Molecular Biology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Tel.: (312) 503-4215. Fax: (312) 503-0954. E-mail: [email protected]
*
Abbreviations used in this paper: IF, intermediate filament; LA, lamin A; LB, lamin B; ΔNLA, amino terminus truncation of human lamin A; NLS, nuclear localization signal; PCNA, proliferating cell nuclear antigen; TBP, TATA binding protein.
Received:
December 12 2001
Accepted:
January 04 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 156 (4): 603–608.
Article history
Received:
December 12 2001
Accepted:
January 04 2002
Citation
Timothy P. Spann, Anne E. Goldman, Chen Wang, Sui Huang, Robert D. Goldman; Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription . J Cell Biol 18 February 2002; 156 (4): 603–608. doi: https://doi.org/10.1083/jcb.200112047
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