A cell-specific enhancer of the mouse. cap alpha. 1-antitrypsin gene has multiple functional regions and corresponding protein-binding sites

Journal Article · Tue Mar 01 04:00:00 EST 1988 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.8.3.1055· OSTI ID:7070741

Grayson, D R; Costa, R H; Xanthopoulos, K G; Darnell, Jr, J E

The authors previously described the isolation and characterization of genomic clones corresponding to the mouse ..cap alpha..1-antitrypsin gene. In this report, the authors analyzed the DNA sequences upstream of the RNA start site that direct hepatoma cell-specific expression of this gene when incorporated into recombinant plasmids. The 160 nucleotides 5' to the cap site direct low-level expression in hepatoma cells, and sequences between -520 and -160 bp upstream of the RNA start site functioned as a cell-specific enhancer of expression both with the ..cap alpha..1-antitrypsin promoter and when combined with a functional BETA-globin promoter. Within the enhancer region, three binding sites for proteins present in hepatoma nuclear extracts were identified. The location of each site was positioned, using both methylation protection and methylation interference experiments. Each protein-binding site correlated with a functionally important region necessary for full enhancer activity. These experiments demonstrated a complex arrangement of regulatory elements comprising the ..cap alpha..1-antitrypsin enhancer. Significant qualitative differences exist between the findings presented here and the cis-acting elements operative in regulating expression of the human ..cap alpha..1-antitrypsin gene.

• Research Organization: The Rockefeller Univ., New York, NY (US)
• OSTI ID: 7070741
• Journal Information: Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 8:3; ISSN MCEBD
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
550400 -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTIBODIES
CELL CONSTITUENTS
CHEMICAL REACTIONS
CLONING
DATA
DISEASES
DNA
DNA SEQUENCING
DNA-CLONING
ENZYME INHIBITORS
ENZYMES
EXPERIMENTAL DATA
GENE OPERONS
GENE REGULATION
GENE REPRESSORS
GENES
GLOBIN
HEPATOMAS
HYDROLASES
INFORMATION
MAMMALS
MESSENGER-RNA
METHYLATION
MICE
NEOPLASMS
NUCLEIC ACIDS
NUCLEOPROTEINS
NUMERICAL DATA
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PHENOTYPE
PLASMIDS
PROTEINS
RECOMBINANT DNA
RNA
RODENTS
SERINE PROTEINASES
SPECIFICITY
STRUCTURAL CHEMICAL ANALYSIS
TRYPSIN
TUMOR CELLS
VERTEBRATES