• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. Oct 11, 1990; 18(19): 5853–5863.
PMCID: PMC332325

A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain.

Abstract

Hepatic Nuclear Factor 1 (HNF1, also referred to as LFB1, HP1 or APF) is a liver-specific transcription factor required for the expression of many hepatocyte specific genes. We report here the purification of this rat liver nuclear protein and the cloning of its cDNA using a PCR-derived approach. Seven independent clones reveal 3 alternative polyadenylation sites and a unique open reading frame. Both a motif homologous to the homeodomain and a distal dimerization domain are required for specific DNA binding. Sequence comparisons reveal several atypical features at key positions in the segment corresponding to helices III and IV of the Antaennapedia homeodomain as well as a potential 24 amino acid loop in place of the universal turn between helices II and III. Together with its property to dimerize in the presence or absence of DNA, these features place HNF1 as the prototype of a novel subclass of transcription factors distantly related to homeoproteins.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Gorski K, Carneiro M, Schibler U. Tissue-specific in vitro transcription from the mouse albumin promoter. Cell. 1986 Dec 5;47(5):767–776. [PubMed]
  • Heard JM, Herbomel P, Ott MO, Mottura-Rollier A, Weiss M, Yaniv M. Determinants of rat albumin promoter tissue specificity analyzed by an improved transient expression system. Mol Cell Biol. 1987 Jul;7(7):2425–2434. [PMC free article] [PubMed]
  • Cereghini S, Raymondjean M, Carranca AG, Herbomel P, Yaniv M. Factors involved in control of tissue-specific expression of albumin gene. Cell. 1987 Aug 14;50(4):627–638. [PubMed]
  • 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. [PubMed]
  • Babiss LE, Herbst RS, Bennett AL, Darnell JE., Jr Factors that interact with the rat albumin promoter are present both in hepatocytes and other cell types. Genes Dev. 1987 May;1(3):256–267. [PubMed]
  • Herbomel P, Rollier A, Tronche F, Ott MO, Yaniv M, Weiss MC. The rat albumin promoter is composed of six distinct positive elements within 130 nucleotides. Mol Cell Biol. 1989 Nov;9(11):4750–4758. [PMC free article] [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]
  • Courtois G, Morgan JG, Campbell LA, Fourel G, Crabtree GR. Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters. Science. 1987 Oct 30;238(4827):688–692. [PubMed]
  • Hardon EM, Frain M, Paonessa G, Cortese R. Two distinct factors interact with the promoter regions of several liver-specific genes. EMBO J. 1988 Jun;7(6):1711–1719. [PMC free article] [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]
  • 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]
  • 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Ryffel GU, Kugler W, Wagner U, Kaling M. Liver cell specific gene transcription in vitro: the promoter elements HP1 and TATA box are necessary and sufficient to generate a liver-specific promoter. Nucleic Acids Res. 1989 Feb 11;17(3):939–953. [PMC free article] [PubMed]
  • 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. [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]
  • Arcangioli B, Pochet S, Sousa R, Huynh-Dinh T. Preparation and use of a universal primed Sepharose for the purification of DNA-binding proteins. Eur J Biochem. 1989 Feb 1;179(2):359–363. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Bauw G, De Loose M, Inzé D, Van Montagu M, Vandekerckhove J. Alterations in the phenotype of plant cells studied by NH(2)-terminal amino acid-sequence analysis of proteins electroblotted from two-dimensional gel-separated total extracts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4806–4810. [PMC free article] [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Chen EY, Seeburg PH. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. [PubMed]
  • Gorman CM, Merlino GT, Willingham MC, Pastan I, Howard BH. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. [PMC free article] [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [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. [PMC free article] [PubMed]
  • Deschatrette J, Weiss MC. Characterization of differentiated and dedifferentiated clones from a rat hepatoma. Biochimie. 1974;56(11-12):1603–1611. [PubMed]
  • Ryseck RP, Hirai SI, Yaniv M, Bravo R. Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature. 1988 Aug 11;334(6182):535–537. [PubMed]
  • Birnstiel ML, Busslinger M, Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. [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]
  • 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]
  • Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. [PubMed]
  • Dingwall C, Laskey RA. Protein import into the cell nucleus. Annu Rev Cell Biol. 1986;2:367–390. [PubMed]
  • Garnier J, Osguthorpe DJ, Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. [PubMed]
  • Gehring WJ. Homeo boxes in the study of development. Science. 1987 Jun 5;236(4806):1245–1252. [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]
  • He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG. Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature. 1989 Jul 6;340(6228):35–41. [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]
  • Qian YQ, Billeter M, Otting G, Müller M, Gehring WJ, Wüthrich K. The structure of the Antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors. Cell. 1989 Nov 3;59(3):573–580. [PubMed]
  • Pabo CO, Sauer RT. Protein-DNA recognition. Annu Rev Biochem. 1984;53:293–321. [PubMed]
  • Herr W, Sturm RA, Clerc RG, Corcoran LM, Baltimore D, Sharp PA, Ingraham HA, Rosenfeld MG, Finney M, Ruvkun G, et al. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. 1988 Dec;2(12A):1513–1516. [PubMed]
  • Levine M, Hoey T. Homeobox proteins as sequence-specific transcription factors. Cell. 1988 Nov 18;55(4):537–540. [PubMed]
  • Hanes SD, Brent R. DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9. Cell. 1989 Jun 30;57(7):1275–1283. [PubMed]
  • Treisman J, Gönczy P, Vashishtha M, Harris E, Desplan C. A single amino acid can determine the DNA binding specificity of homeodomain proteins. Cell. 1989 Nov 3;59(3):553–562. [PubMed]
  • Sauer RT, Smith DL, Johnson AD. Flexibility of the yeast alpha 2 repressor enables it to occupy the ends of its operator, leaving the center free. Genes Dev. 1988 Jul;2(7):807–816. [PubMed]
  • Keleher CA, Goutte C, Johnson AD. The yeast cell-type-specific repressor alpha 2 acts cooperatively with a non-cell-type-specific protein. Cell. 1988 Jun 17;53(6):927–936. [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]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...