Independent regulation of HNF-1 alpha and HNF-1 beta by retinoic acid in F9 teratocarcinoma cells.
Hepatocyte Nuclear Factor-1 alpha (HNF-1 alpha) and HNF-1 beta are homeodomain-containing transcription factors which interact with the GTTAATNATTAAC motif essential to the function of more than 15 promoters selectively expressed in the liver. These homeoproteins can form homo- and heterodimers in solution and share identical DNA-binding domains but have different transcriptional activation properties. During retinoic acid (RA) induced differentiation of F9 embryonal carcinoma (EC) cells, which stimulates aspects of pre-implantation embryogenesis, both HNF-1 beta mRNA and immunoreactive DNA-binding activity are strongly induced approximately 24 h post RA-treatment. In contrast, HNF-1 alpha mRNA increases approximately 4-fold after 5 days, concomitant with elevation of HNF-1 alpha DNA-binding activity and expression of the HNF-1 target gene alpha-fetoprotein. These results indicate that HNF-1 alpha and -1 beta expression can be controlled by regulatory hierarchies downstream of primary RA-response genes, and suggest that independent regulatory mechanisms for these factors can confer distinct and interactive developmental functions.
Kuo
C J
CJ
Howard Hughes Medical Institute, eckman Center, Stanford University School of Medicine, CA 94305-5425.
Mendel
D B
DB
Hansen
L P
LP
Crabtree
G R
GR
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D016172:DNA Fingerprinting; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054278:Embryonal Carcinoma Stem Cells; D005786:Gene Expression Regulation; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D004247:DNA