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. 1993 Nov;12(11):4251–4259. doi: 10.1002/j.1460-2075.1993.tb06109.x

IPF1, a homeodomain-containing transactivator of the insulin gene.

H Ohlsson 1, K Karlsson 1, T Edlund 1
PMCID: PMC413720  PMID: 7901001

Abstract

We describe the cloning of insulin promoter factor 1 (IPF1), a homeodomain protein which in the adult mouse pancreas is selectively expressed in the beta-cells and which binds to and transactivates the insulin promoter. In embryos, IPF1 expression is initiated prior to hormone gene expression and is restricted to the dorsal and ventral walls of the primitive foregut at the positions where pancreas will later form. The pattern of IPF1 expression and its ability to stimulate insulin gene transcription suggest that IPF1 functions both in the regionalization of the primitive gut endoderm and in the maturation of the pancreatic beta-cell.

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Selected References

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

  1. Alpert S., Hanahan D., Teitelman G. Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell. 1988 Apr 22;53(2):295–308. doi: 10.1016/0092-8674(88)90391-1. [DOI] [PubMed] [Google Scholar]
  2. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Cheung A. K. DNA nucleotide sequence analysis of the immediate-early gene of pseudorabies virus. Nucleic Acids Res. 1989 Jun 26;17(12):4637–4646. doi: 10.1093/nar/17.12.4637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Edlund T., Walker M. D., Barr P. J., Rutter W. J. Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5' flanking elements. Science. 1985 Nov 22;230(4728):912–916. doi: 10.1126/science.3904002. [DOI] [PubMed] [Google Scholar]
  6. Efrat S., Linde S., Kofod H., Spector D., Delannoy M., Grant S., Hanahan D., Baekkeskov S. Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9037–9041. doi: 10.1073/pnas.85.23.9037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Efrat S., Teitelman G., Anwar M., Ruggiero D., Hanahan D. Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic alpha cells. Neuron. 1988 Sep;1(7):605–613. doi: 10.1016/0896-6273(88)90110-9. [DOI] [PubMed] [Google Scholar]
  8. Ericson J., Thor S., Edlund T., Jessell T. M., Yamada T. Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1. Science. 1992 Jun 12;256(5063):1555–1560. doi: 10.1126/science.1350865. [DOI] [PubMed] [Google Scholar]
  9. Georgopoulos K., Moore D. D., Derfler B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science. 1992 Oct 30;258(5083):808–812. doi: 10.1126/science.1439790. [DOI] [PubMed] [Google Scholar]
  10. German M. S., Wang J., Chadwick R. B., Rutter W. J. Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex. Genes Dev. 1992 Nov;6(11):2165–2176. doi: 10.1101/gad.6.11.2165. [DOI] [PubMed] [Google Scholar]
  11. Gittes G. K., Rutter W. J. Onset of cell-specific gene expression in the developing mouse pancreas. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1128–1132. doi: 10.1073/pnas.89.3.1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Grillner S., Matsushima T. The neural network underlying locomotion in lamprey--synaptic and cellular mechanisms. Neuron. 1991 Jul;7(1):1–15. doi: 10.1016/0896-6273(91)90069-c. [DOI] [PubMed] [Google Scholar]
  13. Herr W., Sturm R. A., Clerc R. G., Corcoran L. M., Baltimore D., Sharp P. A., Ingraham H. A., Rosenfeld M. G., Finney M., Ruvkun G. 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. doi: 10.1101/gad.2.12a.1513. [DOI] [PubMed] [Google Scholar]
  14. Herrera P. L., Huarte J., Sanvito F., Meda P., Orci L., Vassalli J. D. Embryogenesis of the murine endocrine pancreas; early expression of pancreatic polypeptide gene. Development. 1991 Dec;113(4):1257–1265. doi: 10.1242/dev.113.4.1257. [DOI] [PubMed] [Google Scholar]
  15. Ingraham H. A., Chen R. P., Mangalam H. J., Elsholtz H. P., Flynn S. E., Lin C. R., Simmons D. M., Swanson L., Rosenfeld M. G. A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell. 1988 Nov 4;55(3):519–529. doi: 10.1016/0092-8674(88)90038-4. [DOI] [PubMed] [Google Scholar]
  16. Karlsson O., Edlund T., Moss J. B., Rutter W. J., Walker M. D. A mutational analysis of the insulin gene transcription control region: expression in beta cells is dependent on two related sequences within the enhancer. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8819–8823. doi: 10.1073/pnas.84.24.8819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karlsson O., Thor S., Norberg T., Ohlsson H., Edlund T. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo- and a Cys-His domain. Nature. 1990 Apr 26;344(6269):879–882. doi: 10.1038/344879a0. [DOI] [PubMed] [Google Scholar]
  18. Klempnauer K. H., Sippel A. E. The highly conserved amino-terminal region of the protein encoded by the v-myb oncogene functions as a DNA-binding domain. EMBO J. 1987 Sep;6(9):2719–2725. doi: 10.1002/j.1460-2075.1987.tb02565.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Li S., Crenshaw E. B., 3rd, Rawson E. J., Simmons D. M., Swanson L. W., Rosenfeld M. G. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature. 1990 Oct 11;347(6293):528–533. doi: 10.1038/347528a0. [DOI] [PubMed] [Google Scholar]
  20. Madsen O. D., Larsson L. I., Rehfeld J. F., Schwartz T. W., Lernmark A., Labrecque A. D., Steiner D. F. Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones. J Cell Biol. 1986 Nov;103(5):2025–2034. doi: 10.1083/jcb.103.5.2025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ohlsson H., Edlund T. Sequence-specific interactions of nuclear factors with the insulin gene enhancer. Cell. 1986 Apr 11;45(1):35–44. doi: 10.1016/0092-8674(86)90535-0. [DOI] [PubMed] [Google Scholar]
  22. Ohlsson H., Karlsson O., Edlund T. A beta-cell-specific protein binds to the two major regulatory sequences of the insulin gene enhancer. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4228–4231. doi: 10.1073/pnas.85.12.4228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ohlsson H., Thor S., Edlund T. Novel insulin promoter- and enhancer-binding proteins that discriminate between pancreatic alpha- and beta-cells. Mol Endocrinol. 1991 Jul;5(7):897–904. doi: 10.1210/mend-5-7-897. [DOI] [PubMed] [Google Scholar]
  24. Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Price M., Lazzaro D., Pohl T., Mattei M. G., Rüther U., Olivo J. C., Duboule D., Di Lauro R. Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian forebrain. Neuron. 1992 Feb;8(2):241–255. doi: 10.1016/0896-6273(92)90291-k. [DOI] [PubMed] [Google Scholar]
  26. Ruiz i Altaba A., Jessell T. M. Retinoic acid modifies the pattern of cell differentiation in the central nervous system of neurula stage Xenopus embryos. Development. 1991 Aug;112(4):945–958. doi: 10.1242/dev.112.4.945. [DOI] [PubMed] [Google Scholar]
  27. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  28. Steiner D. F., Chan S. J., Welsh J. M., Kwok S. C. Structure and evolution of the insulin gene. Annu Rev Genet. 1985;19:463–484. doi: 10.1146/annurev.ge.19.120185.002335. [DOI] [PubMed] [Google Scholar]
  29. Teitelman G., Lee J. K. Cell lineage analysis of pancreatic islet development: glucagon and insulin cells arise from catecholaminergic precursors present in the pancreatic duct. Dev Biol. 1987 Jun;121(2):454–466. doi: 10.1016/0012-1606(87)90182-5. [DOI] [PubMed] [Google Scholar]
  30. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  31. Wedeen C. J., Kostriken R. G., Matsumura I., Weisblat D. A. Evidence for a new family of evolutionarily conserved homeobox genes. Nucleic Acids Res. 1990 Apr 11;18(7):1908–1908. doi: 10.1093/nar/18.7.1908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yamada T., Placzek M., Tanaka H., Dodd J., Jessell T. M. Control of cell pattern in the developing nervous system: polarizing activity of the floor plate and notochord. Cell. 1991 Feb 8;64(3):635–647. doi: 10.1016/0092-8674(91)90247-v. [DOI] [PubMed] [Google Scholar]
  33. Yoshinari M., Daikoku S. Ontogenetic appearance of immunoreactive endocrine cells in rat pancreatic islets. Anat Embryol (Berl) 1982 Sep;165(1):63–70. doi: 10.1007/BF00304583. [DOI] [PubMed] [Google Scholar]

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