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Nucleic Acids Res. 1991 July 11; 19(13): 3553–3559.
PMCID: PMC328379

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


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.

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  • Rey-Campos J, Chouard T, Yaniv M, Cereghini S. vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1. EMBO J. 1991 Jun;10(6):1445–1457. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Shaw G, Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. [PubMed]
  • Hope IA, Struhl K. GCN4, a eukaryotic transcriptional activator protein, binds as a dimer to target DNA. EMBO J. 1987 Sep;6(9):2781–2784. [PubMed]
  • Jones N. Transcriptional regulation by dimerization: two sides to an incestuous relationship. Cell. 1990 Apr 6;61(1):9–11. [PubMed]
  • Goutte C, Johnson AD. a1 protein alters the DNA binding specificity of alpha 2 repressor. Cell. 1988 Mar 25;52(6):875–882. [PubMed]
  • Dranginis AM. Binding of yeast a1 and alpha 2 as a heterodimer to the operator DNA of a haploid-specific gene. Nature. 1990 Oct 18;347(6294):682–685. [PubMed]
  • Green S, Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. [PubMed]
  • Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. [PubMed]
  • Lewis EB. A gene complex controlling segmentation in Drosophila. Nature. 1978 Dec 7;276(5688):565–570. [PubMed]
  • Scott MP, Tamkun JW, Hartzell GW., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. [PubMed]
  • Duboule D, Dollé P. The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. EMBO J. 1989 May;8(5):1497–1505. [PubMed]
  • Lalley PA, Davison MT, Graves JA, O'Brien SJ, Womack JE, Roderick TH, Creau-Goldberg N, Hillyard AL, Doolittle DP, Rogers JA. Report of the committee on comparative mapping. Cytogenet Cell Genet. 1989;51(1-4):503–532. [PubMed]
  • Abbott C, Piaggio G, Ammendola R, Solomon E, Povey S, Gounari F, De Simone V, Cortese R. Mapping of the gene TCF2 coding for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction. Genomics. 1990 Sep;8(1):165–167. [PubMed]
  • Fletcher C, Heintz N, Roeder RG. Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene. Cell. 1987 Dec 4;51(5):773–781. [PubMed]
  • Schöler HR, Hatzopoulos AK, Balling R, Suzuki N, Gruss P. A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J. 1989 Sep;8(9):2543–2550. [PubMed]
  • Müller MM, Ruppert S, Schaffner W, Matthias P. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature. 1988 Dec 8;336(6199):544–551. [PubMed]
  • Maniatis T, Goodbourn S, Fischer JA. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. [PubMed]
  • Schorpp M, Kugler W, Wagner U, Ryffel GU. Hepatocyte-specific promoter element HP1 of the Xenopus albumin gene interacts with transcriptional factors of mammalian hepatocytes. J Mol Biol. 1988 Jul 20;202(2):307–320. [PubMed]
  • Tronche F, Rollier A, Bach I, Weiss MC, Yaniv M. The rat albumin promoter: cooperation with upstream elements is required when binding of APF/HNF1 to the proximal element is partially impaired by mutation or bacterial methylation. Mol Cell Biol. 1989 Nov;9(11):4759–4766. [PMC free article] [PubMed]
  • Tronche F, Rollier A, Herbomel P, Bach I, Cereghini S, Weiss M, Yaniv M. Anatomy of the rat albumin promoter. Mol Biol Med. 1990 Apr;7(2):173–185. [PubMed]
  • Courtois G, Baumhueter S, Crabtree GR. 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. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Lichtsteiner S, Schibler U. A glycosylated liver-specific transcription factor stimulates transcription of the albumin gene. Cell. 1989 Jun 30;57(7):1179–1187. [PubMed]
  • Baumhueter S, Mendel DB, Conley PB, Kuo CJ, Turk C, Graves MK, Edwards CA, Courtois G, Crabtree GR. 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. [PubMed]
  • Chouard T, Blumenfeld M, Bach I, Vandekerckhove J, Cereghini S, Yaniv M. A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain. Nucleic Acids Res. 1990 Oct 11;18(19):5853–5863. [PMC free article] [PubMed]
  • Bach I, Galcheva-Gargova Z, Mattei MG, Simon-Chazottes D, Guénet JL, Cereghini S, Yaniv M. Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse. Genomics. 1990 Sep;8(1):155–164. [PubMed]
  • Kuo CJ, Conley PB, Hsieh CL, Francke U, Crabtree GR. Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9838–9842. [PubMed]
  • 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. [PubMed]
  • 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. [PubMed]
  • Cereghini S, Yaniv M, Cortese R. Hepatocyte dedifferentiation and extinction is accompanied by a block in the synthesis of mRNA coding for the transcription factor HNF1/LFB1. EMBO J. 1990 Jul;9(7):2257–2263. [PubMed]
  • Deschatrette J, Weiss MC. Characterization of differentiated and dedifferentiated clones from a rat hepatoma. Biochimie. 1974;56(11-12):1603–1611. [PubMed]
  • Baumhueter S, Courtois G, Crabtree GR. 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. [PubMed]
  • Dressler GR, Gruss P. Do multigene families regulate vertebrate development? Trends Genet. 1988 Aug;4(8):214–219. [PubMed]

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