Abstract
The homeodomain-containing transcription factor hepatocyte nuclear factor 1 (HNF-1) most likely plays an essential role during liver organogenesis by transactivating a family of greater than 15 predominantly hepatic genes. We have isolated cDNA clones encoding mouse HNF-1 and expressed them in monkey COS cells and in the human T-cell line Jurkat, producing HNF-1 DNA-binding activity as well as transactivation of reporter constructs containing multimerized HNF-1 binding sites. In addition, the HNF-1 gene was assigned by somatic cell hybrids and recombinant inbred strain mapping to mouse chromosome 5 near Bcd-1 and to human chromosome 12 region q22-qter, revealing a homologous chromosome region in these two species. The presence of HNF-1 mRNA in multiple endodermal tissues (liver, stomach, intestine) suggests that HNF-1 may constitute an early marker for endodermal, rather than hepatocyte, differentiation. Further, that HNF-1 DNA-binding and transcriptional activity can be conferred by transfecting the HNF-1 cDNA into several cell lines indicates that it is sufficient to activate transcription in the context of ubiquitously expressed factors.
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- Baumhueter S., Courtois G., Crabtree G. R. A variant nuclear protein in dedifferentiated hepatoma cells binds to the same functional sequences in the beta fibrinogen gene promoter as HNF-1. EMBO J. 1988 Aug;7(8):2485–2493. doi: 10.1002/j.1460-2075.1988.tb03095.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baumhueter S., Mendel D. B., Conley P. B., Kuo C. J., Turk C., Graves M. K., Edwards C. A., Courtois G., Crabtree G. R. HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF. Genes Dev. 1990 Mar;4(3):372–379. doi: 10.1101/gad.4.3.372. [DOI] [PubMed] [Google Scholar]
- Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
- Bodner M., Castrillo J. L., Theill L. E., Deerinck T., Ellisman M., Karin M. The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. Cell. 1988 Nov 4;55(3):505–518. doi: 10.1016/0092-8674(88)90037-2. [DOI] [PubMed] [Google Scholar]
- Cereghini S., Blumenfeld M., Yaniv M. A liver-specific factor essential for albumin transcription differs between differentiated and dedifferentiated rat hepatoma cells. Genes Dev. 1988 Aug;2(8):957–974. doi: 10.1101/gad.2.8.957. [DOI] [PubMed] [Google Scholar]
- Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
- Costa R. H., Grayson D. R., Darnell J. E., Jr Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes. Mol Cell Biol. 1989 Apr;9(4):1415–1425. doi: 10.1128/mcb.9.4.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Courtois G., Baumhueter S., Crabtree G. R. Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7937–7941. doi: 10.1073/pnas.85.21.7937. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Courtois G., Morgan J. G., Campbell L. A., Fourel G., Crabtree G. R. Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters. Science. 1987 Oct 30;238(4827):688–692. doi: 10.1126/science.3499668. [DOI] [PubMed] [Google Scholar]
- Feuerman M. H., Godbout R., Ingram R. S., Tilghman S. M. Tissue-specific transcription of the mouse alpha-fetoprotein gene promoter is dependent on HNF-1. Mol Cell Biol. 1989 Oct;9(10):4204–4212. doi: 10.1128/mcb.9.10.4204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finney M. The homeodomain of the transcription factor LF-B1 has a 21 amino acid loop between helix 2 and helix 3. Cell. 1990 Jan 12;60(1):5–6. doi: 10.1016/0092-8674(90)90708-m. [DOI] [PubMed] [Google Scholar]
- Frain M., Swart G., Monaci P., Nicosia A., Stämpfli S., Frank R., Cortese R. The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain. Cell. 1989 Oct 6;59(1):145–157. doi: 10.1016/0092-8674(89)90877-5. [DOI] [PubMed] [Google Scholar]
- Friedman A. D., Landschulz W. H., McKnight S. L. CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells. Genes Dev. 1989 Sep;3(9):1314–1322. doi: 10.1101/gad.3.9.1314. [DOI] [PubMed] [Google Scholar]
- Glass C. K., Lipkin S. M., Devary O. V., Rosenfeld M. G. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell. 1989 Nov 17;59(4):697–708. doi: 10.1016/0092-8674(89)90016-0. [DOI] [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsieh C. L., Sturm R., Herr W., Francke U. The gene for the ubiquitous octamer-binding protein Oct-1 is on human chromosome 1, region cen-q32, and near Ly-22 and Ltw-4 on mouse chromosome 1. Genomics. 1990 Apr;6(4):666–672. doi: 10.1016/0888-7543(90)90502-l. [DOI] [PubMed] [Google Scholar]
- Lalley P. A., Davison M. T., Graves J. A., O'Brien S. J., Womack J. E., Roderick T. H., Creau-Goldberg N., Hillyard A. L., Doolittle D. P., Rogers J. A. Report of the committee on comparative mapping. Cytogenet Cell Genet. 1989;51(1-4):503–532. doi: 10.1159/000132806. [DOI] [PubMed] [Google Scholar]
- Lichtsteiner S., Wuarin J., Schibler U. The interplay of DNA-binding proteins on the promoter of the mouse albumin gene. Cell. 1987 Dec 24;51(6):963–973. doi: 10.1016/0092-8674(87)90583-6. [DOI] [PubMed] [Google Scholar]
- Lin A. Y., Devaux B., Green A., Sagerström C., Elliott J. F., Davis M. M. Expression of T cell antigen receptor heterodimers in a lipid-linked form. Science. 1990 Aug 10;249(4969):677–679. doi: 10.1126/science.1696397. [DOI] [PubMed] [Google Scholar]
- Maire P., Wuarin J., Schibler U. The role of cis-acting promoter elements in tissue-specific albumin gene expression. Science. 1989 Apr 21;244(4902):343–346. doi: 10.1126/science.2711183. [DOI] [PubMed] [Google Scholar]
- Monaci P., Nicosia A., Cortese R. Two different liver-specific factors stimulate in vitro transcription from the human alpha 1-antitrypsin promoter. EMBO J. 1988 Jul;7(7):2075–2087. doi: 10.1002/j.1460-2075.1988.tb03047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
- Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
- Nicosia A., Monaci P., Tomei L., De Francesco R., Nuzzo M., Stunnenberg H., Cortese R. A myosin-like dimerization helix and an extra-large homeodomain are essential elements of the tripartite DNA binding structure of LFB1. Cell. 1990 Jun 29;61(7):1225–1236. doi: 10.1016/0092-8674(90)90687-a. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw J. P., Utz P. J., Durand D. B., Toole J. J., Emmel E. A., Crabtree G. R. Identification of a putative regulator of early T cell activation genes. Science. 1988 Jul 8;241(4862):202–205. doi: 10.1126/science.3260404. [DOI] [PubMed] [Google Scholar]
- Tyner A. L., Godbout R., Compton R. S., Tilghman S. M. The ontogeny of alpha-fetoprotein gene expression in the mouse gastrointestinal tract. J Cell Biol. 1990 Apr;110(4):915–927. doi: 10.1083/jcb.110.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tyner A. L., Godbout R., Compton R. S., Tilghman S. M. The ontogeny of alpha-fetoprotein gene expression in the mouse gastrointestinal tract. J Cell Biol. 1990 Apr;110(4):915–927. doi: 10.1083/jcb.110.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winchester G., Mitchison N. A., Taylor B. A. The structural gene for F liver protein (Flp) maps to chromosome 5 of the mouse. Immunogenetics. 1987;26(6):356–358. doi: 10.1007/BF00343704. [DOI] [PubMed] [Google Scholar]
- Xanthopoulos K. G., Mirkovitch J., Decker T., Kuo C. F., Darnell J. E., Jr Cell-specific transcriptional control of the mouse DNA-binding protein mC/EBP. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4117–4121. doi: 10.1073/pnas.86.11.4117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang-Feng T. L., DeGennaro L. J., Francke U. Genes for synapsin I, a neuronal phosphoprotein, map to conserved regions of human and murine X chromosomes. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8679–8683. doi: 10.1073/pnas.83.22.8679. [DOI] [PMC free article] [PubMed] [Google Scholar]