Abstract
RETINOIC acid has been implicated as a natural morphogen in chicken1–4 and frog5 embryogenesis, and is presumed to act through the gene regulatory activity of a family of nuclear receptors6–10. Homeobox genes, which specify positional information in Drosophila and possibly in vertebrate embryogenesis11–21, are among the candidate responsive genes4,5,14. We previously reported that retinoic acid specifically induces human homeobox gene (HOX) expression in the embryonal carcinoma cell line NT2/D1 (ref. 22). We now show that the nine genes of the HOX2 cluster are differentially activated in NT2/D1 cells exposed to retinoic acid concentrations ranging from 10–8 to 10–5 M. Genes located in the 3' half of the cluster are induced at peak levels by 10–8 M retinoic acid, whereas a concentration of 10–6 to 10–5 M is required to fully activate 5' genes. At both high and low retinoic acid concentrations, HOX2 genes are sequentially activated in embryonal carcinoma cells in the 3' to 5' direction.
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References
Tickle, C. et al. Nature 296, 564–565 (1982).
Thaller, C. & Eichele, G. Nature 327, 625–628 (1987).
Thaller, C. & Eichele, G. Development 103, 473–483 (1988).
Brockes, J.P. Neuron 2, 1285–1294 (1989).
Durston, A. J. et al. Nature 340, 140–144 (1989).
Petkovich, M., Brand, N.J., Krust, A. & Chambon, P. Nature 330, 444–450 (1987).
Giguere, V., Ong, E. S., Sequi, P. & Evans, R. M. Nature 330, 624–629 (1987).
Brand, N. J. et al. Nature 332, 850–853 (1988).
Zelent, A., Krust, A., Petkovich, M., Kastner, P. & Chambon, P. Nature 339, 714–717 (1989).
Mangelsdorf, D. J., Ong, E. S., Dyck, J. A. & Evans, R. M. Nature 345, 224–229 (1990).
Gehring, W. J. Science 236, 1245–1252 (1987).
Ingham, P. W. Nature 335, 25–34 (1988).
Holland, P. W. H. & Hogan, B. L. M. Genes Dev. 2, 773–782 (1988).
De Robertis, E. M., Oliver, G. & Wright V. E. Cell 57, 189–191 (1989).
Simeone, A. et al. Nature 320, 763–765 (1986).
Mavilio, F. et al. Nature 324, 664–668 (1986).
Simeone, A. et al. Proc. natn. Acad. Sci. U.S.A. 84, 4914–4918 (1987).
Graham, A., Papalopulu, N. and Krumlauf, R. Cell 57, 367–378 (1989).
Wilkinson, D. G., Bhatt, S., Cook, M., Boncinelli, E. & Krumlauf, R. Nature 341, 405–409 (1989).
Giampaolo, A. et al. Differentiation 40, 191–197 (1989).
Duboule, D. & Dollè, P. EMBO J. 8, 1497–1505 (1989).
Mavilio, F., Simeone, A., Boncinelli, E. & Andrews, P. W. Differentiation 37, 73–79 (1988).
Andrews, P. W. Devl Biol. 103, 285–293 (1984).
McCormick, A. M. & Napoli, J. L. J. biol. Chem. 257, 1730–1735 (1982).
Matthaei, K. I., Andrews, P. W. & Bronson, D. L. Expl Cell Res. 143, 471–474 (1983).
Acampora, D. et al. Nucleic Acids Res. 17, 10385–10402 (1989).
Chirgwin, J. M. et al. Biochemistry 18, 5294–5300 (1979).
Thomas, P. S. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).
Ponte, P., Gunning, P., Blau, H. & Kedes, L. Molec. cell Biol. 3, 1783–1791 (1983).
Melton, D. A. et al. Nucleic Acids Res. 12, 7035–7056 (1984).
Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor, New York, 1989).
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Simeone, A., Acampora, D., Arcioni, L. et al. Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Nature 346, 763–766 (1990). https://doi.org/10.1038/346763a0
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DOI: https://doi.org/10.1038/346763a0
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