In vivo footprinting analysis of the hepatic control region of the human apolipoprotein E/C-I/C-IV/C-II gene locus.

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  • Author(s): Dang Q;Dang Q; Taylor J
  • Source:
    The Journal of biological chemistry [J Biol Chem] 1996 Nov 08; Vol. 271 (45), pp. 28667-76.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Apolipoproteins C/*genetics ; Apolipoproteins E/*genetics ; Liver/*chemistry; Apolipoprotein C-I ; Apolipoprotein C-II ; Base Sequence ; Chromosome Mapping ; DNA Footprinting ; Deoxyribonuclease I/metabolism ; Electrophoresis, Polyacrylamide Gel ; Genes, Regulator ; Humans ; Molecular Sequence Data
    • Abstract:
      Expression of both the apolipoprotein (apo)E and apoC-I genes in the liver is specified by a 319-nucleotide hepatic control region (HCR-1) that is located 15 kilobase pairs downstream of the apoE gene and 5 kilobase pairs downstream of the apoC-I gene. In vivo footprint analysis of HCR-1 in intact nuclei revealed several liver-specific protein-binding sites that were not detectable by in vitro methods. In addition to three previously identified in vitro footprints, four in vivo footprints were identified in a region of HCR-1 that is required for directing gene expression to hepatocytes. Prominent liver-specific DNase I-hypersensitive sites were associated with these footprints. Liver-specific nuclear protein binding to these sites was confirmed by oligonucleotide gel-retention assays. The in vivo analysis also identified a cluster of nuclear protein-binding sites in the Alu family repeat segment adjacent to the domain required for liver expression. Micrococcal nuclease digestion indicated the presence of a nucleosome in the central domain of HCR-1 in liver chromatin that was in phase with the nucleosome location in tissues that did not express the transgene. These results suggest that HCR-1 functions in a highly structured chromatin environment requiring a complex interaction of liver-enriched transcription factors.
    • Grant Information:
      HL07731 United States HL NHLBI NIH HHS; HL37063 United States HL NHLBI NIH HHS
    • Molecular Sequence:
      GENBANK U35114
    • Accession Number:
      0 (APOC4 protein, human)
      0 (Apolipoprotein C-I)
      0 (Apolipoprotein C-II)
      0 (Apolipoproteins C)
      0 (Apolipoproteins E)
      EC 3.1.21.1 (Deoxyribonuclease I)
    • Publication Date:
      Date Created: 19961108 Date Completed: 19961230 Latest Revision: 20210209
    • Publication Date:
      20231215
    • Accession Number:
      10.1074/jbc.271.45.28667
    • Accession Number:
      8910501