Liver enriched transcription factor

Details Liver enriched transcription factor Liver enriched transcription factor

C - Chemistry, Metallurgy

12

N

C12N 15/62 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) C07H 21/00 (2006.01) C07K 14/435 (2006.01) C07K 14/47 (2006.01) C07K 14/705 (2006.01) C07K 14/72 (2006.01) C07K 16/00 (2006.01) C07K 16/42 (2006.01) C07K 19/00 (2006.01) C12N 15/12 (2006.01) C12N 15/67 (2006.01) C12P 21/08 (2006.01) C12Q 1/48 (2006.01) C12Q 1/66 (2006.01) C12Q 1/68 (2006.01) G01N 33/534 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2098838

HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hor- mone receptor superfamily with an unusal amino acid in the conserved "knuckle" of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF- 4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues. DNA binding data suggest that HNF-4 could be identical to liver Factor A (LF- Al), a factor previously shown to regulate the transcription of the .alpha.-1 antitrypsin, apolipoprotein Al and pyruvate kinase genes.

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