Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors
Apolipoprotein CIII (apoCIII) is a major protein constituent of triglyceride-rich lipoproteins and is synthesized primarily in the liver. Cis-acting DNA elements required for liver-specific apoCIII gene transcription were identified with transient expression assays in the human hepatoma (HepG2) and epithelial carcinoma (HeLa) cell lines. In liver cells, 821 nucleotides of the human apoCIII gene 5'-flanking sequence were required for maximum levels of gene expression, while the proximal 110 nucleotides alone were sufficient. No expression was observed in similar studies with HeLa cells. The level of expression was modulated by a combination of positive and negative cis-acting sequences, which interact with distinct sets of proteins from liver and HeLa cell nuclear extracts. The proximal positive regulatory region shares homology with similarly located sequences of other genes strongly expressed in the liver, including ..cap alpha../sub 1/-antitrypsin and other apolipoprotein genes. The negative regulatory region is striking homologous to the human ..beta..-interferon gene regulatory element. The distal positive region shares homology with some viral enhancers and has properties of a tissue-specific enhancer. The regulation of the apoCIII gene is complex but shares features with other genes, suggesting shuffling of regulatory elements as a common mechanism for cell type-specific gene expression.
- Research Organization:
- Rockefeller Univ., New York, NY (USA)
- OSTI ID:
- 6925118
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 263:14
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
APOLIPOPROTEINS
GENE REGULATION
GENES
DNA SEQUENCING
CARCINOMAS
ENZYME ACTIVITY
HELA CELLS
HEPATOMAS
LIVER
LIVER CELLS
PHOSPHORUS 32
TRANSCRIPTION
TRANSFERASES
TUMOR CELLS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GLANDS
ISOTOPES
LIGHT NUCLEI
LIPIDS
LIPOPROTEINS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
550201* - Biochemistry- Tracer Techniques