ArticleProceedings of the National Academy of Sciences of the United States of America1999
The HNF-4/HNF-1alpha transactivation cascade regulates gene activity and chromatin structure of the human serine protease inhibitor gene cluster at 14q32.1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Molecular alterations associated with pathophysiology in liver-specific ZO-1 and ZO-2 knockout mice.Cell structure and function · 2024Article
- HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements.Communications biology · 2024Article
- BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment.Cell host & microbe · 2020Article
- Hepatocyte Nuclear Factor 4-Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver.Hepatology (Baltimore, Md.) · 2019Article
- Direct conversion of human fibroblasts into hepatocyte-like cells by ATF5, PROX1, FOXA2, FOXA3, and HNF4A transduction.Scientific reports · 2017Article
- Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels.Nature communications · 2015Article
- Article
- Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels.PLoS genetics · 2013Article
- Expression of exogenous human hepatic nuclear factor-1α by a lentiviral vector and its interactions with Plasmodium falciparum subtilisin-like protease 2.The Korean journal of parasitology · 2011Article
- Cooperation between HNF-1alpha, Cdx2, and GATA-4 in initiating an enterocytic differentiation program in a normal human intestinal epithelial progenitor cell line.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver.PPAR research · 2010Article
- The locus control region activates serpin gene expression through recruitment of liver-specific transcription factors and RNA polymerase II.Molecular and cellular biology · 2007Article
- Astrocyte- and hepatocyte-specific expression of genes from the distal serpin subcluster at 14q32.1 associates with tissue-specific chromatin structures.Journal of neurochemistry · 2005Article
- Formation of a large, complex domain of histone hyperacetylation at human 14q32.1 requires the serpin locus control region.Nucleic acids research · 2005Article
- Identification and functional characterization of a novel mutation of hepatocyte nuclear factor-1alpha gene in a Korean family with MODY3.Diabetologia · 2003Article
- Hepatic nuclear factor 1-alpha directs nucleosomal hyperacetylation to its tissue-specific transcriptional targets.Molecular and cellular biology · 2001Article
- Interleukin-6-induced STAT3 and AP-1 amplify hepatocyte nuclear factor 1-mediated transactivation of hepatic genes, an adaptive response to liver injury.Molecular and cellular biology · 2001Article
- Stable expression and cell-specific chromatin structure of human alpha1-antitrypsin cosmid transgenes in rat hepatoma cells.Nucleic acids research · 2000Article
- Differential regulation of gene activity and chromatin structure within the human serpin gene cluster at 14q32.1 in macrophage microcell hybrids.Nucleic acids research · 2000Article
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2 authors at 1 institution in 1 country.
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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.
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