Published online 7 June 2005
Article |
Formation of a large, complex domain of histone hyperacetylation at human 14q32.1 requires the serpin locus control region
Division of Basic Sciences, Fred Hutchinson Cancer Research Center 1100 Fairview Avenue N., Seattle WA, 98109-1024, USA
*To whom correspondence should be addressed. Tel: +1 206 667 5217; Fax: +1 206 667 6522; Email: kfournie{at}fhcrc.org
Received April 25, 2005. Revised May 20, 2005. Accepted May 20, 2005.
The human serine protease inhibitor (serpin) gene cluster at 14q32.1 is a useful model system to study cell-type-specific gene expression and chromatin structure. Activation of the serpin locus can be induced in vitro by transferring human chromosome 14 from non-expressing to expressing cells. Serpin gene activation in expressing cells is correlated with locus-wide alterations in chromatin structure, including the de novo formation of 17 expression-associated DNase I-hypersensitive sites (DHSs). In this study, we investigated histone acetylation throughout the proximal serpin subcluster. We report that gene activation is correlated with high levels of histone H3 and H4 acetylation at serpin gene promoters and other regulatory regions. However, the locus is not uniformly hyperacetylated, as there are regions of hypoacetylation between genes. Furthermore, genetic tests indicate that locus-wide controls regulate both gene expression and chromatin structure. For example, deletion of a previously identified serpin locus control region (LCR) upstream of the proximal subcluster reduces both gene expression and histone acetylation throughout the 
130 kb region. A similar down regulation phenotype is displayed by transactivator-deficient cell variants, but this phenotype can be rescued by transfecting the cells with expression cassettes encoding hepatocyte nuclear factor-1
(HNF-1) or HNF-4. Taken together, these results suggest that histone acetylation depends on interactions between the HNF-1/HNF-4 signaling cascade and the serpin LCR.
Present address: Euan W. Baxter, Molecular Medicine Unit, Clinical Research Building, St. James University Hospital, Leeds, LS9 7TF, UK
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. R. Bowers, F. Mirabella, F. J. Calero-Nieto, S. Valeaux, S. Hadjur, E. W. Baxter, M. Merkenschlager, and P. N. Cockerill A Conserved Insulator That Recruits CTCF and Cohesin Exists between the Closely Related but Divergently Regulated Interleukin-3 and Granulocyte-Macrophage Colony-Stimulating Factor Genes Mol. Cell. Biol., April 1, 2009; 29(7): 1682 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhao, R. D. Friedman, and R. E. K. Fournier The Locus Control Region Activates Serpin Gene Expression through Recruitment of Liver-Specific Transcription Factors and RNA Polymerase II Mol. Cell. Biol., August 1, 2007; 27(15): 5286 - 5295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Bert, B. V. Johnson, E. W. Baxter, and P. N. Cockerill A Modular Enhancer Is Differentially Regulated by GATA and NFAT Elements That Direct Different Tissue-Specific Patterns of Nucleosome Positioning and Inducible Chromatin Remodeling Mol. Cell. Biol., April 15, 2007; 27(8): 2870 - 2885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Gopalan, K. M. Wilczynska, B. S. Konik, L. Bryan, and T. Kordula Astrocyte-specific Expression of the {alpha}1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes Requires Activator Protein-1 J. Biol. Chem., January 27, 2006; 281(4): 1956 - 1963. [Abstract] [Full Text] [PDF]
|
|