Murine hoxd4 expression in the CNS requires multiple elements including a retinoic acid response element.
We have identified a retinoic acid response element (RARE) within a neural enhancer located 3' to the Hoxd4 gene. This RARE is required for the initiation and maintenance of Hoxd4 transgene expression in neurectoderm, and for full anteriorized expression upon retinoic acid (RA) treatment. Mutations within the sequence TTTTCTG, located 2 bp downstream of the RARE, posteriorized transgene activity. However, the onset of transgene expression and its response to RA were indistinguishable from wild type. While the TTTTCTG motif resembles a CDX binding site, human CDX1 protein did not interact with this element in vitro. Three additional regions were also shown to control transgene expression in neurectoderm, establishing that multiple elements constitute the Hoxd4 neural enhancer.
McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Québec H3G 1Y6, Montréal, Canada.
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Zhang
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Nagy Kovács
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MS
Featherstone
D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D001665:Binding Sites; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism*; D002874:Chromosome Mapping; D004247:DNA / Q000378:metabolism; D004475:Ectoderm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004622:Embryo, Mammalian / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020218:Response Elements; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D019076:Transgenes; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
D030161:Avian Proteins; C491273:CDX1 protein, human; C491272:Cdx1 protein, mouse; D018398:Homeodomain Proteins; C489520:Hoxd4 protein, mouse; D014157:Transcription Factors; C072064:HOXD10 protein, human; D014212:Tretinoin; D004247:DNA; D001616:beta-Galactosidase