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Vitamin D-dependent recruitment of DNA-PK to the chromatinized negative vitamin D response element in the PTHrP gene is required for gene repression by vitamin D.

Abstract：

:The mechanism of transcriptional repression by nuclear hormone receptors, especially in the presence of the ligands, is largely unknown. We previously reported that 1,25-dihydroxyvitamin D(3) (1,25 vitamin D3) inhibited expression of the parathyroid hormone-related polypeptide (PTHrP) gene through the interaction between the liganded monomeric vitamin D receptor (VDR) and the negative DNA element in the PTHrP gene (nVDRE(RP)). In this study, we employed chromatin immunoprecipitation (ChIP) assay and confirmed that 1,25 vitamin D3 recruited DNA-dependent protein kinase (DNA-PKcs) to the chromatinized nVDRE(RP). Conversely, the regulatory subunits of DNA-PK were associated with the nVDRE(RP) sequences only when 1,25 vitamin D3 was absent. VDR was constitutively associated with these chromatinized nVDRE(RP) sequences. Furthermore, DNA-PKcs could phosphorylate VDR in vitro. We raise a possibility that a conformational change of VDR through its phosphorylation mediated by DNA-PKcs underlies the mechanism of gene repression by 1,25 vitamin D3-bound VDR.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Okazaki T,Nishimori S,Ogata E,Fujita T

doi

10.1016/s0006-291x(03)00651-x

subject

Has Abstract

pub_date

2003-05-16 00:00:00

pages

632-7

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006291X0300651X

journal_volume

304

pub_type

杂志文章

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