Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alcohol Oxidoreductases / metabolism
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Amino Acid Sequence
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Base Sequence
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Binding Sites
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Breast Neoplasms / genetics*
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Cell Line, Tumor
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Chromatin Assembly and Disassembly
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Chromatin Immunoprecipitation
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DNA-Binding Proteins / metabolism
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Female
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Gene Expression Regulation, Neoplastic*
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Histone Deacetylase 1
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Histone Deacetylases / metabolism
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Humans
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Molecular Sequence Data
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Promoter Regions, Genetic
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Protein Binding
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Receptors, Calcitriol / genetics*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Snail Family Transcription Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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DNA-Binding Proteins
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Receptors, Calcitriol
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Repressor Proteins
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SNAI1 protein, human
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Snail Family Transcription Factors
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Transcription Factors
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Alcohol Oxidoreductases
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C-terminal binding protein
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylases