Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and. alpha. 1-antitrypsin genes

Journal Article · Sat Apr 01 00:00:00 EST 1989 · Molecular and Cellular Biology; (USA)

DOI:https://doi.org/10.1128/MCB.9.4.1415· OSTI ID:5516954

Costa, R H ^[1]; Grayson, D R ^[1]; Darnell, Jr, J E ^[2]

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1. Dept. of Anatomy and Cell Biology, Georgetown Medical School, FIDIA-Georgetown Institute for the Neurosciences, Washington, DC (US)
2. Rockefeller Univ., New York, NY (USA)

Transthyretin (TTR) and {alpha}1-antitrypsin ({alpha}1-AT) are expressed at high levels in the liver and also in at least one other cell type. The authors report here a detailed analysis of the proximal regulatory region of the TTR gene, which has uncovered two new DNA-binding factors that are present mainly (or only) in hepatocytes. One of these new factors, hepatocyte nuclear factor 3 (HNF-3), binds to two sites that are crucial in TTR expression as well as to two additional sites in the {alpha}1-AT proximal enhancer region. The second new factor, HNF-4, binds to two sites in TTR that are required for gene activity. The authors had previously identified binding sites for another hepatocyte-enriched DNA-binding protein (C/EBP or a relative thereof), and additional promoter-proximal sites for that protein in both TTR and {alpha}1-AT are also reported here. From these results it seems clear that cell-specific expression is not simply the result of a single cell-specific factor for each gene but the results of a combination of such factors. The variation and distribution of such factors among different cell types could be an important basis for the coordinate expression of the TTR and {alpha}1-AT genes in the liver or the discordant transcriptional activation of these genes in a few other cell types. The identification of such cell-enriched factors is a necessary prelude to understanding the basis for cell specificity.

• OSTI ID: 5516954
• Journal Information: Molecular and Cellular Biology; (USA), Vol. 9:4; ISSN 0270-7306
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
LIVER CELLS
BIOLOGICAL FUNCTIONS
TRANSCRIPTION
BIOLOGICAL PATHWAYS
BIOCHEMICAL REACTION KINETICS
DNA
GENE REPRESSORS
GENES
PHENOTYPE
PROTEINS
SYNTHESIS
TRYPSIN
ANIMAL CELLS
ENZYMES
FUNCTIONS
HYDROLASES
KINETICS
NUCLEIC ACIDS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
REACTION KINETICS
SERINE PROTEINASES
SOMATIC CELLS
550200* - Biochemistry