This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pöpperl, H Articles by Featherstone, M S Search for Related Content PubMed PubMed Citation Articles by Pöpperl, H Articles by Featherstone, M S

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 January; 13(1): 257-265

Identification of a retinoic acid response element upstream of the murine Hox-4.2 gene.

McGill Cancer Centre, Montréal, Québec, Canada.

ABSTRACT

Hox genes play an important role in the process of vertebrate pattern formation, and their expression is intricately regulated both temporally and spatially. All-trans-retinoic acid (RA), a physiologically active metabolite of vitamin A, affects the expression of a large number of Hox genes in vitro and in vivo. However, the regulatory mechanisms underlying the RA response of these genes have not been extensively studied, and no response element for RA receptors (RARs) has been characterized in a Hox regulatory region. The expression of murine Hox-4.2 and its human homolog, HOX4B, is increased in embryonal carcinoma (EC) cell lines upon RA treatment (M. S. Featherstone, A. Baron, S. J. Gaunt, M.-G. Mattei, and D. Duboule, Proc. Natl. Acad. Sci. USA 85:4760-4764, 1988; A. Simeone, D. Acampora, V. Nigro, A. Faiella, M. D'Esposito, A. Stornaiuolo, F. Mavilio, and E. Boncinelli, Mech. Dev. 33:215-228, 1991). Using transient expression assays, we showed that luciferase reporter gene constructs carrying genomic sequences located upstream of Hox-4.2 responded to RA in murine P19 EC cells. A 402-bp NcoI fragment was necessary for the RA responsiveness of reporter constructs. This fragment contained a regulatory element, 5'-AGGTGA(N)5AGGTCA-3', that closely resembles the consensus sequence for an RA response element. The Hox-4.2 RA response element was critical for the RA induction and specifically bound RARs. In addition, the response to RA could be inhibited by expressing a dominant negative form of RAR alpha in transfected P19 EC cells. These results suggested that Hox-4.2 is a target for RAR-mediated regulation by RA.

This article has been cited by other articles:

• Boffa, M. B., Maret, D., Hamill, J. D., Bastajian, N., Crainich, P., Jenny, N. S., Tang, Z., Macy, E. M., Tracy, R. P., Franco, R. F., Nesheim, M. E., Koschinsky, M. L. (2008). Effect of single nucleotide polymorphisms on expression of the gene encoding thrombin-activatable fibrinolysis inhibitor: a functional analysis. Blood 111: 183-189 [Abstract] [Full Text]  
• Chen, H., Zhang, H., Lee, J., Liang, X., Wu, X., Zhu, T., Lo, P.-k., Zhang, X., Sukumar, S. (2007). HOXA5 Acts Directly Downstream of Retinoic Acid Receptor {beta} and Contributes to Retinoic Acid Induced Apoptosis and Growth Inhibition. Cancer Res. 67: 8007-8013 [Abstract] [Full Text]  
• Kobrossy, L., Rastegar, M., Featherstone, M. (2006). Interplay between Chromatin and Trans-acting Factors Regulating the Hoxd4 Promoter during Neural Differentiation. J. Biol. Chem. 281: 25926-25939 [Abstract] [Full Text]  
• Daftary, G. S., Taylor, H. S. (2006). Endocrine Regulation of HOX Genes. Endocr. Rev. 27: 331-355 [Abstract] [Full Text]  
• Purton, L. E., Dworkin, S., Olsen, G. H., Walkley, C. R., Fabb, S. A., Collins, S. J., Chambon, P. (2006). RAR{gamma} is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation. J. Exp. Med. 203: 1283-1293 [Abstract] [Full Text]  
• Qin, P., Haberbusch, J. M., Zhang, Z., Soprano, K. J., Soprano, D. R. (2004). Pre-B Cell Leukemia Transcription Factor (PBX) Proteins Are Important Mediators for Retinoic Acid-dependent Endodermal and Neuronal Differentiation of Mouse Embryonal Carcinoma P19 Cells. J. Biol. Chem. 279: 16263-16271 [Abstract] [Full Text]  
• Dupe, V., Lumsden, A. (2001). Hindbrain patterning involves graded responses to retinoic acid signalling. Development 128: 2199-2208 [Abstract] [Full Text]  
• Saleh, M., Rambaldi, I., Yang, X.-J., Featherstone, M. S. (2000). Cell Signaling Switches HOX-PBX Complexes from Repressors to Activators of Transcription Mediated by Histone Deacetylases and Histone Acetyltransferases. Mol. Cell. Biol. 20: 8623-8633 [Abstract] [Full Text]  
• Houle, M., Prinos, P., Iulianella, A., Bouchard, N., Lohnes, D. (2000). Retinoic Acid Regulation of Cdx1: an Indirect Mechanism for Retinoids and Vertebral Specification. Mol. Cell. Biol. 20: 6579-6586 [Abstract] [Full Text]  
• Ross, S. A., McCaffery, P. J., Drager, U. C., De Luca, L. M. (2000). Retinoids in Embryonal Development. Physiol. Rev. 80: 1021-1054 [Abstract] [Full Text]  
• Huang, D, Chen, S., Langston, A., Gudas, L. (1998). A conserved retinoic acid responsive element in the murine Hoxb-1 gene is required for expression in the developing gut. Development 125: 3235-3246 [Abstract]  
• Packer, A., Crotty, D., Elwell, V., Wolgemuth, D. (1998). Expression of the murine Hoxa4 gene requires both autoregulation and a conserved retinoic acid response element. Development 125: 1991-1998 [Abstract]  
• Studer, M, Gavalas, A, Marshall, H, Ariza-McNaughton, L, Rijli, F., Chambon, P, Krumlauf, R (1998). Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning. Development 125: 1025-1036 [Abstract]  
• van der Wees, J, Schilthuis, J., Koster, C., Diesveld-Schipper, H, Folkers, G., van der Saag, P., Dawson, M., Shudo, K, van der Burg, B, Durston, A. (1998). Inhibition of retinoic acid receptor-mediated signalling alters positional identity in the developing hindbrain. Development 125: 545-556 [Abstract]  
• Folberg, A., Kovacs, E. N., Featherstone, M. S. (1997). Characterization and Retinoic Acid Responsiveness of the Murine Hoxd4 Transcription Unit. J. Biol. Chem. 272: 29151-29157 [Abstract] [Full Text]  
• Cash, D. E., Bock, C. B., Schughart, K., Linney, E., Underhill, T. M. (1997). Retinoic Acid Receptor alpha  Function in Vertebrate Limb Skeletogenesis: a Modulator of Chondrogenesis. J. Cell Biol. 136: 445-457 [Abstract] [Full Text]  
• Langston, A. W., Thompson, J. R., Gudas, L. J. (1997). Retinoic Acid-responsive Enhancers Located 3' of the Hox A and Hox B Homeobox Gene Clusters. FUNCTIONAL ANALYSIS. J. Biol. Chem. 272: 2167-2175 [Abstract] [Full Text]  
• Morrison, A, Ariza-McNaughton, L, Gould, A, Featherstone, M, Krumlauf, R (1997). HOXD4 and regulation of the group 4 paralog genes. Development 124: 3135-3146 [Abstract]  
• Core, N, Bel, S, Gaunt, S., Aurrand-Lions, M, Pearce, J, Fisher, A, Djabali, M (1997). Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice. Development 124: 721-729 [Abstract]  
• Dupe, V, Davenne, M, Brocard, J, Dolle, P, Mark, M, Dierich, A, Chambon, P, Rijli, F. (1997). In vivo functional analysis of the Hoxa-1 3' retinoic acid response element (3'RARE). Development 124: 399-410 [Abstract]  
• Lawrence, H., Sauvageau, G, Humphries, R., Largman, C (1996). The role of HOX homeobox genes in normal and leukemic hematopoiesis. Stem Cells 14: 281-291 [Abstract]  
• Morrison, A, Moroni, M., Ariza-McNaughton, L, Krumlauf, R, Mavilio, F (1996). In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer. Development 122: 1895-1907 [Abstract]  
• Knittel, T, Kessel, M, Kim, M., Gruss, P (1995). A conserved enhancer of the human and murine Hoxa-7 gene specifies the anterior boundary of expression during embryonal development. Development 121: 1077-1088 [Abstract]  
• Studer, M, Popperl, H, Marshall, H, Kuroiwa, A, Krumlauf, R (1994). Role of a conserved retinoic acid response element in rhombomere restriction of Hoxb-1. Science 265: 1728-1732 [Abstract]  
• Lohnes, D, Mark, M, Mendelsohn, C, Dolle, P, Dierich, A, Gorry, P, Gansmuller, A, Chambon, P (1994). Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. Development 120: 2723-2748 [Abstract]  
• Taira, M, Otani, H, Jamrich, M, Dawid, I. (1994). Expression of the LIM class homeobox gene Xlim-1 in pronephros and CNS cell lineages of Xenopus embryos is affected by retinoic acid and exogastrulation. Development 120: 1525-1536 [Abstract]  
• Davidson, E. (1993). Later embryogenesis: regulatory circuitry in morphogenetic fields. Development 118: 665-690 [Abstract]