The role of a retinoic acid response element in establishing the anterior neural expression border of Hoxd4 transgenes.
The zebrafish hoxd4a locus was compared to its murine ortholog, Hoxd4. The sequence of regulatory elements, including a DR5 type retinoic acid response element (RARE) required for Hoxd4 neural enhancer activity, are highly conserved. Additionally, zebrafish and mouse neural enhancers function identically in transgenic mouse embryos. We tested whether sequence conservation reflects functional importance by altering the spacing and sequence of the RARE in the Hoxd4 neural enhancer. Stabilizing receptor-DNA interactions did not anteriorize transgene expression. By contrast, conversion of the RARE from a DR5 to a DR2 type element decreased receptor-DNA stability and posteriorized expression. Hence, the setting of the Hox anterior expression border is not a simple function of the affinity of retinoid receptors for their cognate element.
Nolte
Christof
C
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Amores
Angel
A
Nagy Kovács
Erzsébet
E
Postlethwait
John
J
Featherstone
Mark
M
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D017124:Conserved Sequence; D019281:Dimerization; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006207:Half-Life; D018398:Homeodomain Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009420:Nervous System / Q000196:embryology*; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes; D014212:Tretinoin / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; C489520:Hoxd4 protein, mouse; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; D029961:Zebrafish Proteins; C099223:hoxd10a protein, zebrafish; D014212:Tretinoin; D001616:beta-Galactosidase