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Letters to Nature

Nature 346, 763-766 (23 August 1990) | doi:10.1038/346763a0; Received 27 October 1989; Accepted 7 June 1990

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†§

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