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Cited by 42Genomics and Chromatin DynamicsLiver physiology and pathologyChromatin Remodeling and Cancer

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

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Rollini, Pierre, Fournier, R. E. K.·1999·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.96.18.10308PMC PMC17884
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Abstract

Hepatocyte-specific expression of the α1-antitrypsin (α1AT) gene requires the activities of two liver-enriched transactivators, hepatocyte nuclear factors 1α and 4 (HNF-1α and HNF-4). The α1AT 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 ≈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 α1AT and CBG transcription and chromatin reorganization of the entire locus. To assess the roles of HNF-1α 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-1α and HNF-4. The variant cells failed to activate either α1AT or CBG transcription, and chromatin remodeling failed to occur. However, α1AT and CBG transcription could be rescued by transfecting the cells with expression plasmids encoding HNF-1α or HNF-4. In these transfectants, the chromatin structure of the entire α1AT/CBG locus was reorganized to an expressing cell-typical state. Thus, HNF-1α 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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  • Ectopic HNF4A expression in fibroblasts induces DNase1 hypersensitivity of the Serpin gene cluster at 14q32.1 to transcriptionally regulate α1-antitrypsin and corticosteroid binding globulin.

    “Previous studies have suggested that HNF4A plays multiple roles in chromatin reorganization: ectopic HNF4A expression in fibroblasts was shown to induce DNase1 hypersensitivity of the Serpin gene cluster at 14q32.1 to transcriptionally regulate α1-antitrypsin and corticosteroid binding globulin (39).”

    From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [39]

    The Results report that HNF-4 expression induced DNase I-hypersensitive sites and rescued α1-antitrypsin and CBG expression in transactivator-deficient hepatoma hybrids, not fibroblasts. The Discussion explicitly says that rat fibroblast α1-antitrypsin genes are refractory to activation by HNF-4, contrary to the claimed fibroblast result. (LLM, conf=0.88)

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  • HNF4A plays a role in the establishment of active enhancers.

    “This supports a role of HNF4A in the establishment of active enhancers(39).”

    From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [39]

    The Results report that introducing HNF-4 induced expression-associated DNase I hypersensitive sites and established active-locus chromatin structure in the α1AT/ATR/CBG region (page unavailable). However, the Discussion says the functions of individual regulatory elements remain to be defined. The paper supports a role in chromatin remodeling, but does not establish that the induced sites are active enhancers. (LLM, conf=0.85)

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  1. [16]Elgin S C R. J Biol Chem. 1988;263:19259–19262. [PubMed] [Google Scholar]
  2. [27]Cereghini S. FASEB J. 1996;10:267–282. [PubMed] [Google Scholar]
  3. [32]Mendel D B, Crabtree G R. J Biol Chem. 1991;266:677–680. [PubMed] [Google Scholar]
  4. [41]Potempa J, Korzus E, Travis J. J Biol Chem. 1994;269:15957–15960. [PubMed] [Google Scholar]
  5. [55]Hohn P A, Popescu N C, Hanson R D, Salvesen G, Ley T J. J Biol Chem. 1989;264:13412–13419. [PubMed] [Google Scholar]

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Authors
Rollini, P., & Fournier, R. E. K.
Affiliations
Fred Hutch Cancer Center (US)
ORCID
Fournier, R. E. K.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1999-08-31
Volume
96
Issue
18
Pages
10308-10313
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.96.18.10308
PMC
PMC17884
OpenAlex
W2013667233
Cited by
42
References
66
Citations by year
2025: 1 · 2024: 1 · 2020: 1 · 2019: 2 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 3
FWCI
1.38
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM 26449, R01GM026449)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
HNF1A, HNF4, alpha-1-antitrypsin, corticosteroid-binding globulin, chromatin remodeling, DNase I hypersensitive sites, hepatocyte-specific gene expression, transcriptional activation, rat hepatoma cells, liver-enriched transcription factors
MeSH terms
Animals, Chromatin, Chromosome Mapping, Chromosomes, Human, Pair 14, DNA-Binding Proteins, Fibroblasts, Gene Expression Regulation, Multigene Family, Humans, Liver Neoplasms, Experimental, Nuclear Proteins, Phosphoproteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Transcriptional Activation, Serpins, Rats, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Hepatocyte Nuclear Factor 4, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors

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