Hepatocyte Nuclear Factor-4 Is Responsible for the Liver-specific Expression of the Gene Coding for Hepatocyte Growth Factor-like Protein (∗)

• Published in: The Journal of biological chemistry 1996-04, Vol.271 (15), p.9024-9032
• Main Authors: Waltz, Susan E., Gould, Fiona K., Air, Ellen L., McDowell, Susan A., Degen, Sandra J. Friezner
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Binding Sites; Cloning, Molecular; DNA Primers - chemistry; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Genes; Growth Substances - genetics; Hepatocyte Growth Factor; Hepatocyte Nuclear Factor 4; Liver - physiology; Molecular Sequence Data; Phosphoproteins - physiology; Promoter Regions, Genetic; Proto-Oncogene Proteins; Restriction Mapping; Structure-Activity Relationship; Transcription Factors - physiology; Transcriptional Activation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.15.9024

In an attempt to understand the molecular mechanism regulating the expression of the gene coding for human hepatocyte growth factor-like protein/macrophage stimulating protein (HGFL), our laboratory has isolated and characterized approximately 4200 bp of the 5′-flanking region of the HGFL gene. To determine the location of sites which may be critical for the function of the HGFL gene promoter, we constructed a series of hybrid genes containing serial deletions of this region attached to the coding sequences for chloramphenicol acetyltransferase. Expression of these chimeric plasmids was examined by transient transfection of HepG2 and 293 cells. Our results suggest that the transcriptional activity of the HGFL promoter is modulated in HepG2 cells by one positive element at position −135 to −105 (−135/-105). In contrast, only background levels of chloramphenicol acetyltransferase expression have been detected in 293 cells. The −135/-105 region appears to bind a liver-specific transcription factor essential for expression of this gene. Gel mobility shift experiments with antibodies against hepatocyte nuclear factor-4 (HNF-4) and transactivation of the HGFL promoter by a HNF-4 cDNA expression vector suggest that HNF-4 binds to the −135/-105 region and is responsible for the liver-specific expression of HGFL.