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The transcription factor LF-A1 interacts with a bipartite recognition sequence in the promoter regions of several
D P Ramji1, M H Tadros, E M Hardon
1European Molecular Biology Laboratory, Heidelberg, FRG.
Abstract:
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.