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Nucleic Acids Research, 1991, Vol. 19, No. 13 3553-3559
© 1991

GENOME STRUCTURE AND MAPPING

Two members of an HNF1 homeoprotein family are expressed in human liver

Ingolf Bach, Marie-Geneviéve Mattei1, Silvia Cereghini+ and Moshe Yaniv*

Unité des Virus Oncogènes, UA 041149 du CNRS, Département des Biotechnologies, Institut Pasteur 25 rue du Dr Roux, 75724 Paris Cedex 15 1INSERM U242 Hôpitai d'enfants de la Timone 13385 Marseille Cedex, France

*To whom correspondence should be addressed

Received April 15, 1991. Revised June 4, 1991. Accepted June 4, 1991.

HNF1 is a transcriptional activator, required for the liver-specific expression of a variety of genes, that binds to DNA as a dimer via the most diverged homeodomain known so far. We were Interested to examine whether HNF1 is a unique homeoprotein example or whether it is the prototype of a new subfamily of homeodomain containing proteins. in this work we describe the isolation of a cDNA clone from a human liver library encoding a protein, highly homologous to HNF1 in three regions, including the homeo- and dimerization domains. We show that this protein can heterodimerize with human HNF1 in vitro. Sequence comparison of our clone with a rat variant HNF1 (vHNF1) clone, isolated in parallel in our laboratory from the dedifferentiated H5 hepatoma cell line, identified our cDNA as human vHNF1. vHNF1 is a nuclear protein recognizing the same binding site as HNF1 and previously thought to occur only in dedifferentiated hepatoma cells that fail to express most liver specific genes. Nevertheless, we show by Northern blot analysis that vHNF1 transcripts are present in differentiated human HepG2 hepatoma cells as well as in rat liver and that this transcript level is 10–20 fold lower than that of HNF1. We assigned the vHNF-1 gene to human chromosome 17 and murine chromosome 11. These chromosomal localizations differ from that of the HNF-1 gene indicating that both genes are not clustered on the genome.

+Present address: Unité de Génétique de la Différenciation, Départment de Biologie Moléculaire, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France


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