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Nucleic Acids Research, 1991, Vol. 19, No. 5 1139-1146
© 1991

MOLECULAR BIOLOGY

The transcription factor LF-A1 interacts with a bipartite recognition sequence in the promoter regions of several liver-specific genes

Dipak P. Ramji1,*, Monier H. Tadros1,2, Elizabeth M. Hardon1 and Riccardo Cortese1,+

1European Molecular Biology Laboratory Meyerhofstrasse 1, 6900 Heidelberg 2Institute of Biology 2, Microbiology Schaenzlestrasse 1, 7880 Freiburg, FRG

* To whom correspondence should be addressed

Received July 13, 1990. Revised September 25, 1990. Accepted September 25, 1990.

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.

+ Present address: IRBM, Via Pontina Km 30.600, Pomezia, Rome, Italy


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