TY - JOUR
T1 - An essential set of basic DNA response elements is required for receptor-dependent transcription of the lecithin:retinol acyltransferase (Lrat) gene
AU - Zolfaghari, Reza
AU - Ross, A. Catharine
N1 - Funding Information:
We thank Dr. Nan-qian Li for assistance with animal studies. This work was supported by NIH Grant CA-90214.
PY - 2009/9
Y1 - 2009/9
N2 - 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 ∼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 RARα, RARβ or RARγ, with RXRα, 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.
AB - 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 ∼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 RARα, RARβ or RARγ, with RXRα, 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.
UR - https://www.scopus.com/pages/publications/69849086128
UR - https://www.scopus.com/pages/publications/69849086128#tab=citedBy
U2 - 10.1016/j.abb.2009.08.001
DO - 10.1016/j.abb.2009.08.001
M3 - Article
C2 - 19665987
AN - SCOPUS:69849086128
SN - 0003-9861
VL - 489
SP - 1
EP - 9
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1-2
ER -