An essential role of the CAAT/enhancer binding protein-alpha in the vitamin D-induced expression of the human steroid/bile acid-sulfotransferase ( SULT2A1).
The vitamin D receptor (VDR) regulates steroid and drug metabolism by inducing the genes encoding phase I and phase II enzymes. SULT2A1 is a liver- and intestine-expressed sulfo-conjugating enzyme that converts the alcohol-OH of neutral steroids, bile acids, and drugs to water-soluble sulfated metabolites. 1alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces SULT2A1 gene transcription after the recruitment of VDR to the vitamin D-responsive chromatin region of SULT2A1. A composite element in human SULT2A1 directs the 1,25-(OH)2D3-mediated induction of natural and heterologous promoters. This element combines a VDR/retinoid X receptor-alpha-binding site [vitamin D response element (VDRE)], which is an imperfect inverted repeat 2 of AGCTCA, and a CAAT/enhancer binding protein (C/EBP)-binding site located 9 bp downstream to VDRE. The binding sites were identified by EMSA, antibody supershift, and deoxyribonuclease I footprinting. C/ EBP-alpha at the composite element plays an essential role in the VDR regulation of SULT2A1, because 1) induction was lost for promoters with inactivating mutations at the VDRE or C/ EBP element; 2) SULT2A1 induction by 1,25-(OH)2D3 in C/ EBP-alpha-deficient cells required the expression of cotransfected C/ EBP-alpha; and 3) C/ EBP-beta did not substitute for C/ EBP-alpha in this regulation. VDR and C/ EBP-alpha were recruited concurrently to the composite element along with the coactivators p300, steroid receptor coactivator 1 ( SRC-1), and SRC-2, but not SRC-3. VDR and C/ EBP-alpha associated endogenously as a DNA-dependent, coimmunoprecipitable complex, which was detected at a markedly higher level in 1,25-(OH)2D3-treated cells. These results provide the first example of the essential role of the interaction in cis between C/ EBP-alpha and VDR in directing 1,25-(OH)2D3-induced expression of a VDR target gene.[1]References
- An essential role of the CAAT/enhancer binding protein-alpha in the vitamin D-induced expression of the human steroid/bile acid-sulfotransferase (SULT2A1). Song, C.S., Echchgadda, I., Seo, Y.K., Oh, T., Kim, S., Kim, S.A., Cho, S., Shi, L., Chatterjee, B. Mol. Endocrinol. (2006) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
