Differential regulation by retinoic acid of the homeobox genes of the four HOX loci in human embryonal carcinoma cells

• Published in: Mechanisms of development Vol. 33; no. 3; pp. 215 - 227
• Main Authors: Simeone, Antonio, Acampora, Dario, Nigro, Vincenzo, Faiella, Antonio, D'Esposito, Maurizio, Stornaiuolo, Anna, Mavilio, Fulvio, Boncinelli, Edoardo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.1991
• Subjects: Amino Acid Sequence; Base Sequence; Cells, Cultured; Chromosome Mapping; Cloning, Molecular; Embryonal Carcinoma Stem Cells; Gene Expression Regulation, Neoplastic - drug effects; Genes, Homeobox - drug effects; Genomic Library; Homeobox gene; HOX loci; Humans; Molecular Sequence Data; Neoplastic Stem Cells - drug effects; RNA, Neoplasm - analysis; Sequence Homology, Nucleic Acid; Transcriptional Activation; Tretinoin - pharmacology; Homeobox gene; HOX loci
• ISSN: 0925-4773; 1872-6356
• DOI: 10.1016/0925-4773(91)90029-6

We studied the expression of 38 human homeobox genes belonging to the four HOX complex loci in embryonal carcinoma (EC) cells induced to differentiate by culturing them in a medium containing retinoic acid (RA). Genes located at the 3′ end of each one of the four HOX loci are activated by RA in a sequential order colinear with their 3′ to 5′ arrangement in the cluster: 3′ HOX genes respond early to the drug while upstream genes respond progressively later. Among the genes located at the 5′ end of HOX loci RNase protection analysis reveals that one HOX3 gene and four HOX4 genes are weakly expressed in EC stem cells and downregulated upon treatment with 10 −5 M RA. While activation of early responding genes does not require continuous protein synthesis, the observed timing and polarity of gene activation is disrupted in the absence of protein synthesis.