In vivo binding to and functional repression of the VDR gene promoter by SLUG in human breast cells.

Mittal MK, Myers JN, Misra S, Bailey CK, Chaudhuri G
Biochem Biophys Res Commun. 2008 372 (1): 30-4

PMID: 18485278 · PMCID: PMC2846599 · DOI:10.1016/j.bbrc.2008.04.187

The regulation of vitamin D receptor (VDR), a key mediator in the vitamin D pathway, in breast cancer etiology has long been of interest. We have shown here that the transcriptional repressor protein SLUG inhibits the expression of VDR in human breast cancer cells. To explore the possibility that SLUG regulates the VDR gene promoter, we cloned a 628bp fragment (-613 to +15) of the human VDR gene promoter. This region contains three E2-box sequences (CAGGTG/CACCTG), the classical binding site of SLUG. SLUG specifically inhibited VDR gene promoter activity. Chromatin-immunoprecipitation (ChIP) assays revealed that SLUG is recruited on the native VDR gene promoter along with the co-repressor protein CtBP1 and the effector protein HDAC1. These data suggests that SLUG binds to the E2-box sequences of the VDR gene promoter and recruits CtBP1 and HDAC1, which results in the inhibition of VDR gene expression by chromatin remodeling.

MeSH Terms (21)

Alcohol Oxidoreductases Amino Acid Sequence Base Sequence Binding Sites Breast Neoplasms Cell Line, Tumor Chromatin Assembly and Disassembly Chromatin Immunoprecipitation DNA-Binding Proteins Female Gene Expression Regulation, Neoplastic Histone Deacetylase 1 Histone Deacetylases Humans Molecular Sequence Data Promoter Regions, Genetic Protein Binding Receptors, Calcitriol Repressor Proteins Snail Family Transcription Factors Transcription Factors

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