Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1991 Jun;10(6):1435–1443. doi: 10.1002/j.1460-2075.1991.tb07664.x

LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia.

V De Simone 1, L De Magistris 1, D Lazzaro 1, J Gerstner 1, P Monaci 1, A Nicosia 1, R Cortese 1
PMCID: PMC452805  PMID: 1673925

Abstract

We have cloned and characterized a mouse cDNA coding for LFB3, a DNA binding protein containing an extra-large homeodomain. The first 315 amino acids of LFB3 are highly homologous to the DNA binding domain of LFB1, a regulatory protein involved in the expression of several liver-specific genes. LFB3 is a transcriptional activator which binds to DNA as a dimer and forms heterodimers with LFB1 both in vitro and in vivo. However, LFB3 expression seems not to be directly correlated with the liver-specific phenotype, since it is detected in dedifferentiated hepatoma cell lines which express neither LFB1 nor several liver-specific genes. LFB3 expression starts before that of LFB1 during mouse and rat development, and is strongly increased upon retinoic acid induced differentiation of F9 embryonic carcinoma cells. LFB3 and LFB1 are expressed in the epithelial component of many organs of endodermal and mesodermal origin, suggesting that they may play a more general role associated with the differentiation of specialized epithelia.

Full text

PDF
1435

Images in this article

1436Image
on p.1436
1437Image
on p.1437
1437Image
on p.1437
1438Image
on p.1438
1439Image
on p.1439
1440Image
on p.1440
1440Image
on p.1440

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. 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]
  3. Birkenmeier E. H., Gwynn B., Howard S., Jerry J., Gordon J. I., Landschulz W. H., McKnight S. L. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev. 1989 Aug;3(8):1146–1156. doi: 10.1101/gad.3.8.1146. [DOI] [PubMed] [Google Scholar]
  4. Busch S. J., Sassone-Corsi P. Dimers, leucine zippers and DNA-binding domains. Trends Genet. 1990 Feb;6(2):36–40. doi: 10.1016/0168-9525(90)90071-d. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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. doi: 10.1002/j.1460-2075.1990.tb07396.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  8. Cockerill P. N., Klinken S. P. Octamer-binding proteins in diverse hemopoietic cells. Mol Cell Biol. 1990 Mar;10(3):1293–1296. doi: 10.1128/mcb.10.3.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. De Simone V., Ciliberto G., Hardon E., Paonessa G., Palla F., Lundberg L., Cortese R. Cis- and trans-acting elements responsible for the cell-specific expression of the human alpha 1-antitrypsin gene. EMBO J. 1987 Sep;6(9):2759–2766. doi: 10.1002/j.1460-2075.1987.tb02570.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Deschatrette J., Moore E. E., Dubois M., Weiss M. C. Dedifferentiated variants of a rat hepatoma:reversion analysis. Cell. 1980 Apr;19(4):1043–1051. doi: 10.1016/0092-8674(80)90095-1. [DOI] [PubMed] [Google Scholar]
  13. Descombes P., Chojkier M., Lichtsteiner S., Falvey E., Schibler U. LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. Genes Dev. 1990 Sep;4(9):1541–1551. doi: 10.1101/gad.4.9.1541. [DOI] [PubMed] [Google Scholar]
  14. Dranginis A. M. 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. doi: 10.1038/347682a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Gebhardt R., Ebert A., Bauer G. Heterogeneous expression of glutamine synthetase mRNA in rat liver parenchyma revealed by in situ hybridization and Northern blot analysis of RNA from periportal and perivenous hepatocytes. FEBS Lett. 1988 Dec 5;241(1-2):89–93. doi: 10.1016/0014-5793(88)81037-8. [DOI] [PubMed] [Google Scholar]
  18. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. 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. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Guazzi S., Price M., De Felice M., Damante G., Mattei M. G., Di Lauro R. Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity. EMBO J. 1990 Nov;9(11):3631–3639. doi: 10.1002/j.1460-2075.1990.tb07574.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hardon E. M., 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. doi: 10.1002/j.1460-2075.1988.tb03000.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jones N. Transcriptional regulation by dimerization: two sides to an incestuous relationship. Cell. 1990 Apr 6;61(1):9–11. doi: 10.1016/0092-8674(90)90207-u. [DOI] [PubMed] [Google Scholar]
  22. Kimura A., Israël A., Le Bail O., Kourilsky P. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell. 1986 Jan 31;44(2):261–272. doi: 10.1016/0092-8674(86)90760-9. [DOI] [PubMed] [Google Scholar]
  23. Klinkert M. Q., Herrmann R., Schaller H. Surface proteins of Mycoplasma hyopneumoniae identified from an Escherichia coli expression plasmid library. Infect Immun. 1985 Aug;49(2):329–335. doi: 10.1128/iai.49.2.329-335.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Lai E., Prezioso V. R., Smith E., Litvin O., Costa R. H., Darnell J. E., Jr HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. Genes Dev. 1990 Aug;4(8):1427–1436. doi: 10.1101/gad.4.8.1427. [DOI] [PubMed] [Google Scholar]
  26. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
  27. Lichtsteiner S., Schibler U. A glycosylated liver-specific transcription factor stimulates transcription of the albumin gene. Cell. 1989 Jun 30;57(7):1179–1187. doi: 10.1016/0092-8674(89)90055-x. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. McKnight S. L., Lane M. D., Gluecksohn-Waelsch S. Is CCAAT/enhancer-binding protein a central regulator of energy metabolism? Genes Dev. 1989 Dec;3(12B):2021–2024. doi: 10.1101/gad.3.12b.2021. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Mueller C. R., Maire P., Schibler U. DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. Cell. 1990 Apr 20;61(2):279–291. doi: 10.1016/0092-8674(90)90808-r. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Ptashne M., Gann A. A. Activators and targets. Nature. 1990 Jul 26;346(6282):329–331. doi: 10.1038/346329a0. [DOI] [PubMed] [Google Scholar]
  34. Rodriguez-Boulan E., Nelson W. J. Morphogenesis of the polarized epithelial cell phenotype. Science. 1989 Aug 18;245(4919):718–725. doi: 10.1126/science.2672330. [DOI] [PubMed] [Google Scholar]
  35. Romeo P. H., Prandini M. H., Joulin V., Mignotte V., Prenant M., Vainchenker W., Marguerie G., Uzan G. Megakaryocytic and erythrocytic lineages share specific transcription factors. Nature. 1990 Mar 29;344(6265):447–449. doi: 10.1038/344447a0. [DOI] [PubMed] [Google Scholar]
  36. Schorpp M., Kugler W., Wagner U., Ryffel G. U. 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. doi: 10.1016/0022-2836(88)90460-3. [DOI] [PubMed] [Google Scholar]
  37. Scott M. P., Tamkun J. W., Hartzell G. W., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. doi: 10.1016/0304-419x(89)90033-4. [DOI] [PubMed] [Google Scholar]
  38. Sharp Z. D., Cao Z. Regulation of cell-type-specific transcription and differentiation of the pituitary. Bioessays. 1990 Feb;12(2):80–85. doi: 10.1002/bies.950120206. [DOI] [PubMed] [Google Scholar]
  39. Simeone A., Acampora D., Arcioni L., Andrews P. W., Boncinelli E., Mavilio F. Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature. 1990 Aug 23;346(6286):763–766. doi: 10.1038/346763a0. [DOI] [PubMed] [Google Scholar]
  40. Tepass U., Theres C., Knust E. crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell. 1990 Jun 1;61(5):787–799. doi: 10.1016/0092-8674(90)90189-l. [DOI] [PubMed] [Google Scholar]
  41. Toniatti C., Demartis A., Monaci P., Nicosia A., Ciliberto G. Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites. EMBO J. 1990 Dec;9(13):4467–4475. doi: 10.1002/j.1460-2075.1990.tb07897.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Toth L. E., Slawin K. L., Pintar J. E., Nguyen-Huu M. C. Region-specific expression of mouse homeobox genes in the embryonic mesoderm and central nervous system. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6790–6794. doi: 10.1073/pnas.84.19.6790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tronche F., Rollier A., Bach I., Weiss M. C., 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. doi: 10.1128/mcb.9.11.4759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. de Simone V., Cortese R. The transcriptional regulation of liver-specific gene expression. Oxf Surv Eukaryot Genes. 1988;5:51–90. [PubMed] [Google Scholar]
  45. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES