An essential set of basic DNA response elements is required for receptor-dependent transcription of the lecithin:retinol acyltransferase (Lrat) gene.
Lecithin:retinol acyltransferase (LRAT) is essential for vitamin A storage. Nuclear run-on assays demonstrated transcriptional regulation of the Lrat gene in vivo by all-trans-retinoic acid (RA) and other retinoids. Analysis of a 2.5 kb segment of rat genomic DNA revealed that the region approximately 300 bp upstream from the transcription start site (TSS) is necessary for high luciferase (Luc) reporter activity in HEK293T and HepG2 cells. Although this region lacks retinoid receptor binding elements, it responded to the nuclear receptors RARalpha, RARbeta or RARgamma, with RXRalpha, with and without ligand. Removal of -111 bp from the TSS, which is well conserved in human, rat and mouse genomes, completely eliminated activity. This region contains several basic elements (TATA box, SP3 site, AP-1 site, CAAT box), all of which were essential. Nuclear extracts from RA-treated cells exhibited enhanced binding. Therefore, this proximal region together with basal transcription factors may be sufficient to drive Lrat expression.
Zolfaghari
Reza
R
Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
Ross
A Catharine
AC
D000217:Acyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015894:Genome, Human / Q000502:physiology*; D006801:Humans; D051379:Mice; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics; D016385:TATA Box / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism
D018168:Receptors, Retinoic Acid; D014801:Vitamin A; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase