The HNF-4/HNF-1alpha transactivation cascade regulates gene activity and chromatin structure of the human serine protease inhibitor gene cluster at 14q32.1.

Details

Serval ID
serval:BIB_4B42716E7A80
Type
Article: article from journal or magazin.
Collection
Publications
Title
The HNF-4/HNF-1alpha transactivation cascade regulates gene activity and chromatin structure of the human serine protease inhibitor gene cluster at 14q32.1.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Rollini P., Fournier R.E.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Publication state
Published
Issued date
1999
Volume
96
Number
18
Pages
10308-10313
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
Hepatocyte-specific expression of the alpha1-antitrypsin (alpha1AT) gene requires the activities of two liver-enriched transactivators, hepatocyte nuclear factors 1alpha and 4 (HNF-1alpha and HNF-4). The alpha1AT gene maps to a region of human chromosome 14q32.1 that includes a related serine protease inhibitor (serpin) gene encoding corticosteroid-binding globulin (CBG), and the chromatin organization of this approximately 130-kb region, as defined by DNase I-hypersensitive sites, has been described. Microcell transfer of human chromosome 14 from fibroblasts to rat hepatoma cells results in activation of alpha1AT and CBG transcription and chromatin reorganization of the entire locus. To assess the roles of HNF-1alpha and HNF-4 in gene activation and chromatin remodeling, we transferred human chromosome 14 from fibroblasts to rat hepatoma cell variants that are deficient in expression of HNF-1alpha and HNF-4. The variant cells failed to activate either alpha1AT or CBG transcription, and chromatin remodeling failed to occur. However, alpha1AT and CBG transcription could be rescued by transfecting the cells with expression plasmids encoding HNF-1alpha or HNF-4. In these transfectants, the chromatin structure of the entire alpha1AT/CBG locus was reorganized to an expressing cell-typical state. Thus, HNF-1alpha and HNF-4 control both chromatin structure and gene activity of two cell-specific genes within the serpin gene cluster at 14q32.1.
Keywords
Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Chromatin/genetics, Chromosome Mapping, Chromosomes, Human, Pair 14, DNA-Binding Proteins/metabolism, Fibroblasts/metabolism, Gene Expression Regulation, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Hepatocyte Nuclear Factor 4, Humans, Liver Neoplasms, Experimental/genetics, Multigene Family, Nuclear Proteins, Phosphoproteins/metabolism, Rats, Serpins/genetics, Transcription Factors/metabolism, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Pubmed
Web of science
Create date
11/11/2011 11:11
Last modification date
20/08/2019 13:59
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