Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1992 Nov 11;20(21):5729–5735. doi: 10.1093/nar/20.21.5729

The regulation of the murine Hox-2.5 gene expression during cell differentiation.

T Kondo 1, N Takahashi 1, M Muramatsu 1
PMCID: PMC334409  PMID: 1360646

Abstract

The mouse Hox-2.5 gene containing a Drosophila Antennapedia-type homeobox sequence is expressed in a spatially and temporally restricted manner during embryogenesis. We found that the mouse embryonal carcinoma cell line P19 expresses Hox-2.5 during differentiation by the treatment with retinoic acid (RA). Expression of the Hox-2.5 gene was not detected in undifferentiated P19 cells, but detected 72 hours after treatment with RA. In order to analyze this inductive response, we first identified the Hox-2.5 transcription initiation site and a possible promoter region. Subsequently, we prepared constructs containing various Hox-2.5 DNA fragments fused to a firefly luciferase reporter gene and transfected these into undifferentiated or differentiating P19 cells. These studies have demonstrated that a region -279 to +15 with respect to the transcription initiation site has a differentiation-responsive promoter activity. Deletion analysis suggests that the sequences responsible for this induction are located in several distinct domains within the 294 bp promoter region. Two of the possible differentiation-responsive elements were identified by analysis of DNA-protein interactions, and in vivo competition assays lend support to the notion that these regions are involved in the differential expression of Hox-2.5 promoter activity.

Full text

PDF
5729

Images in this article

5731Image
on p.5731
5732Image
on p.5732
5733Image
on p.5733

Selected References

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

  1. Bogarad L. D., Utset M. F., Awgulewitsch A., Miki T., Hart C. P., Ruddle F. H. The developmental expression pattern of a new murine homeo box gene: Hox-2.5. Dev Biol. 1989 Jun;133(2):537–549. doi: 10.1016/0012-1606(89)90056-0. [DOI] [PubMed] [Google Scholar]
  2. Chavrier P., Vesque C., Galliot B., Vigneron M., Dollé P., Duboule D., Charnay P. The segment-specific gene Krox-20 encodes a transcription factor with binding sites in the promoter region of the Hox-1.4 gene. EMBO J. 1990 Apr;9(4):1209–1218. doi: 10.1002/j.1460-2075.1990.tb08228.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Colberg-Poley A. M., Püschel A. W., Dony C., Voss S. D., Gruss P. Post-transcriptional regulation of a murine homeobox gene transcript in F9 embryonal carcinoma cells. Differentiation. 1987;35(3):206–211. doi: 10.1111/j.1432-0436.1987.tb00170.x. [DOI] [PubMed] [Google Scholar]
  6. 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. doi: 10.1002/j.1460-2075.1989.tb03534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Durston A. J., Timmermans J. P., Hage W. J., Hendriks H. F., de Vries N. J., Heideveld M., Nieuwkoop P. D. Retinoic acid causes an anteroposterior transformation in the developing central nervous system. Nature. 1989 Jul 13;340(6229):140–144. doi: 10.1038/340140a0. [DOI] [PubMed] [Google Scholar]
  8. Fujita T., Sakakibara J., Sudo Y., Miyamoto M., Kimura Y., Taniguchi T. Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-beta gene regulatory elements. EMBO J. 1988 Nov;7(11):3397–3405. doi: 10.1002/j.1460-2075.1988.tb03213.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gorman C. M., Rigby P. W., Lane D. P. Negative regulation of viral enhancers in undifferentiated embryonic stem cells. Cell. 1985 Sep;42(2):519–526. doi: 10.1016/0092-8674(85)90109-6. [DOI] [PubMed] [Google Scholar]
  10. Graham A., Papalopulu N., Krumlauf R. The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell. 1989 May 5;57(3):367–378. doi: 10.1016/0092-8674(89)90912-4. [DOI] [PubMed] [Google Scholar]
  11. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  12. Izpisúa-Belmonte J. C., Tickle C., Dollé P., Wolpert L., Duboule D. Expression of the homeobox Hox-4 genes and the specification of position in chick wing development. Nature. 1991 Apr 18;350(6319):585–589. doi: 10.1038/350585a0. [DOI] [PubMed] [Google Scholar]
  13. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  14. Kress C., Vogels R., De Graaff W., Bonnerot C., Meijlink F., Nicolas J. F., Deschamps J. Hox-2.3 upstream sequences mediate lacZ expression in intermediate mesoderm derivatives of transgenic mice. Development. 1990 Aug;109(4):775–786. doi: 10.1242/dev.109.4.775. [DOI] [PubMed] [Google Scholar]
  15. McGinnis W., Hart C. P., Gehring W. J., Ruddle F. H. Molecular cloning and chromosome mapping of a mouse DNA sequence homologous to homeotic genes of Drosophila. Cell. 1984 Oct;38(3):675–680. doi: 10.1016/0092-8674(84)90262-9. [DOI] [PubMed] [Google Scholar]
  16. McGinnis W., Levine M. S., Hafen E., Kuroiwa A., Gehring W. J. A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. 1984 Mar 29-Apr 4Nature. 308(5958):428–433. doi: 10.1038/308428a0. [DOI] [PubMed] [Google Scholar]
  17. McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
  18. Nohno T., Noji S., Koyama E., Ohyama K., Myokai F., Kuroiwa A., Saito T., Taniguchi S. Involvement of the Chox-4 chicken homeobox genes in determination of anteroposterior axial polarity during limb development. Cell. 1991 Mar 22;64(6):1197–1205. doi: 10.1016/0092-8674(91)90274-3. [DOI] [PubMed] [Google Scholar]
  19. Odenwald W. F., Garbern J., Arnheiter H., Tournier-Lasserve E., Lazzarini R. A. The Hox-1.3 homeo box protein is a sequence-specific DNA-binding phosphoprotein. Genes Dev. 1989 Feb;3(2):158–172. doi: 10.1101/gad.3.2.158. [DOI] [PubMed] [Google Scholar]
  20. Püschel A. W., Balling R., Gruss P. Separate elements cause lineage restriction and specify boundaries of Hox-1.1 expression. Development. 1991 May;112(1):279–287. doi: 10.1242/dev.112.1.279. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Simeone A., Acampora D., Nigro V., Faiella A., D'Esposito M., Stornaiuolo A., Mavilio F., Boncinelli E. Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells. Mech Dev. 1991 Mar;33(3):215–227. doi: 10.1016/0925-4773(91)90029-6. [DOI] [PubMed] [Google Scholar]
  23. Tabin C. J. Retinoids, homeoboxes, and growth factors: toward molecular models for limb development. Cell. 1991 Jul 26;66(2):199–217. doi: 10.1016/0092-8674(91)90612-3. [DOI] [PubMed] [Google Scholar]
  24. Umesono K., Murakami K. K., Thompson C. C., Evans R. M. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell. 1991 Jun 28;65(7):1255–1266. doi: 10.1016/0092-8674(91)90020-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Whiting J., Marshall H., Cook M., Krumlauf R., Rigby P. W., Stott D., Allemann R. K. Multiple spatially specific enhancers are required to reconstruct the pattern of Hox-2.6 gene expression. Genes Dev. 1991 Nov;5(11):2048–2059. doi: 10.1101/gad.5.11.2048. [DOI] [PubMed] [Google Scholar]
  26. Wilkinson D. G., Bhatt S., Cook M., Boncinelli E., Krumlauf R. Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature. 1989 Oct 5;341(6241):405–409. doi: 10.1038/341405a0. [DOI] [PubMed] [Google Scholar]
  27. Zakany J., Tuggle C. K., Patel M. D., Nguyen-Huu M. C. Spatial regulation of homeobox gene fusions in the embryonic central nervous system of transgenic mice. Neuron. 1988 Oct;1(8):679–691. doi: 10.1016/0896-6273(88)90167-5. [DOI] [PubMed] [Google Scholar]
  28. Zwartkruis F., Hoeijmakers T., Deschamps J., Meijlink F. Characterization of the murine Hox-2.3 promoter: involvement of the transcription factor USF (MLTF). Mech Dev. 1991 Mar;33(3):179–190. doi: 10.1016/0925-4773(91)90026-3. [DOI] [PubMed] [Google Scholar]
  29. 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 Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES