This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Marsden, M. D.
Right arrow Articles by Fournier, R. E. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marsden, M. D.
Right arrow Articles by Fournier, R. E. K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2003, p. 3516-3526, Vol. 23, No. 10
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.10.3516-3526.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Chromosomal Elements Regulate Gene Activity and Chromatin Structure of the Human Serpin Gene Cluster at 14q32.1

Mark D. Marsden and R. E. K. Fournier*

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109

Received 30 October 2002/ Returned for modification 19 December 2002/ Accepted 28 February 2003

The human serine protease inhibitor (serpin) gene cluster at 14q32.1 contains a number of genes that are specifically expressed in hepatic cells. Cell-specific enhancers have been identified in several of these genes, but elements involved in locus-wide gene and chromatin control have yet to be defined. To identify regulatory elements in this region, we prepared a series of mutant chromosomal alleles by homologous recombination and transferred the specifically modified human chromosomes to hepatic cells for functional tests. We report that deletion of an 8-kb DNA segment upstream of the human {alpha}1-antitrypsin gene yields a mutant serpin allele that fails to be activated in hepatic cells. Within this region, a 2.3-kb DNA segment between kb -8.1 and -5.8 contains a previously unrecognized control region that is required not only for serpin gene activation but also for chromatin remodeling of the entire locus.

* Corresponding author. Mailing address: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109. Phone: (206) 667-5217. Fax: (206) 667-6522. E-mail: kfournie{at}fhcrc.org.

Molecular and Cellular Biology, May 2003, p. 3516-3526, Vol. 23, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.10.3516-3526.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhao, H., Friedman, R. D., Fournier, R. E. K. (2007). The Locus Control Region Activates Serpin Gene Expression through Recruitment of Liver-Specific Transcription Factors and RNA Polymerase II. Mol. Cell. Biol. 27: 5286-5295 [Abstract] [Full Text]  
  • Gopalan, S. M., Wilczynska, K. M., Konik, B. S., Bryan, L., Kordula, T. (2006). Astrocyte-specific Expression of the {alpha}1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes Requires Activator Protein-1. J. Biol. Chem. 281: 1956-1963 [Abstract] [Full Text]  
  • Mijalski, T., Harder, A., Halder, T., Kersten, M., Horsch, M., Strom, T. M., Liebscher, H. V., Lottspeich, F., de Angelis, M. H., Beckers, J. (2005). Identification of coexpressed gene clusters in a comparative analysis of transcriptome and proteome in mouse tissues. Proc. Natl. Acad. Sci. USA 102: 8621-8626 [Abstract] [Full Text]  
  • Baxter, E. W., Cummings, W. J., Fournier, R. E. K. (2005). Formation of a large, complex domain of histone hyperacetylation at human 14q32.1 requires the serpin locus control region. Nucleic Acids Res 33: 3313-3322 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»