The transcription factor LF-A1 interacts with a bipartite recognition sequence in the promoter regions of several liver-specific genes.
The transcription factors LF-A1 and LF-B1 are required for the cell-specific expression of the human alpha 1-antitrypsin gene in hepatocytes. We report here the purification and preliminary characterization of LF-A1. This protein, purified to homogeneity from calf liver nuclei by site-specific DNA affinity chromatography and reverse-phase HPLC, has a molecular mass of 40 kDa. Binding sites of LF-A1 are present in the promoter regions of several genes expressed in the liver (alpha 1-antitrypsin, apolipoproteins A1, B1, A4 and pyruvate kinase). Interestingly, the binding site of LF-A1 is bipartite and consists of two short sequence motifs (consensus: TGGACT/CT/C and TGGCCC) separated by a variable 'spacer' region. Insertion or deletion of 1-4 nucleotides in the 'spacer' region of the site in the alpha 1-antitrypsin promoter does not abolish DNA binding.
Ramji
D P
DP
European Molecular Biology Laboratory, Heidelberg, FRG.
Tadros
M H
MH
Hardon
E M
EM
Cortese
R
R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D004247:DNA; D004268:DNA-Binding Proteins; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D004247:DNA