A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes.
Double-stranded oligodeoxynucleotides that represent protein binding sites in the regulatory regions of the mouse genes encoding transthyretin (TTR) and alpha 1-antitrypsin (alpha 1-AT) bound a nuclear protein factor(s) found mainly in hepatocytes. A site in the regulatory region of the gene encoding rat serum albumin and, surprisingly, a region in the simian virus 40 enhancer also bind the same factor. Oligodeoxynucleotide affinity chromatography (with one of the TTR binding sites) allowed a 500-fold purification of the protein. The purified protein protected similar portions of all the regulatory regions, as well as the simian virus 40 core C enhancer element, from digestion with DNase I. A DNA-binding protein previously purified from liver by virtue of its ability to bind to several virus enhancer sequences also binds to TTR, alpha 1-AT, and albumin regulatory sites. Thus, all these binding sites, which contain only minimal sequence similarity, may bind to a single protein, or a similar family of proteins, that activates liver-specific transcription of coordinately expressed genes.
Costa
R H
RH
Rockefeller University, New York, NY 10021.
Grayson
D R
DR
Xanthopoulos
K G
KG
Darnell
J E
JE
D000418:Albumins / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D008099:Liver / Q000502:physiology*; D011228:Prealbumin / Q000235:genetics*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D000418:Albumins; D004268:DNA-Binding Proteins; D011228:Prealbumin; D014157:Transcription Factors; D000515:alpha 1-Antitrypsin