Nature 346, 763 - 766 (23 August 1990); doi:10.1038/346763a0

Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells

Antonio Simeone^*, Dario Acampora^*, Laura Arcioni^†, Peter W. Andrews^‡, Edoardo Boncinelli^* & Fulvio Mavilio^†§

^*International Institute of Genetics and Biophysics, CNR, Via Marconi 10, 80125 Napoli, Italy
^†Istituto Scientifico H. S. Raffaele, Via Olgettina 60, 20132 Milano, Italy
^‡The Wistar Institute, 36th and Spruce Streets, Philadelphia, Pennsylvania 19104, USA
^§To whom correspondence should be addressed.

RETINOIC acid has been implicated as a natural morphogen in chicken^1–4 and frog⁵ embryogenesis, and is presumed to act through the gene regulatory activity of a family of nuclear receptors^6–10. Homeobox genes, which specify positional information in Drosophila and possibly in vertebrate embryogenesis^11–21, are among the candidate responsive genes^4,5,14. 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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