Open AccessRegulation of relB in dendritic cells by means of modulated association of vitamin D receptor and histone deacetylase 3 with the promoter
Author(s) -
Xiangyang Dong,
Ward Lutz,
Tania M. Schroeder,
Lori A. Bachman,
Jennifer J. Westendorf,
Rajiv Kumar,
Matthew D. Griffin
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0506516102
Subject(s) - relb , calcitriol receptor , hdac3 , trichostatin a , histone deacetylase , histone deacetylase 2 , chemistry , chromatin remodeling , microbiology and biotechnology , chromatin immunoprecipitation , cancer research , transcription factor , receptor , biology , histone , promoter , nfkb1 , biochemistry , gene expression , gene
The NF-κB component RelB is essential for dendritic cell (DC) differentiation and maturation. The vitamin D receptor (VDR) is a nuclear receptor that mediates inhibition of DC maturation and transcriptional repression ofrelB after engagement of its ligand, 1α,25-dihydroxyvitamin D3 , or related analogs (D3 analogs). Ligand-dependentrelB suppression was abolished by a histone deacetylase (HDAC) inhibitor. Constitutive association of VDR with therelB promoter was demonstrated in DCs by chromatin immunoprecipitation. Promoter binding by VDR was enhanced by ligand and reduced by LPS. Association of HDAC3 and HDAC1 with therelB VDR-binding site was observed, but only HDAC3 was reciprocally modulated by D3 analog and LPS. Overexpression of HDAC3 causedrelB promoter suppression, increased sensitivity to D3 analog, and resistance to LPS. Depletion of HDAC3 attenuatedrelB suppression by D3 analog.In vivo , D3 analog resulted in reduced RelB in DCs from VDR WT mice but not VDR knockout mice. Other NF-lation of RelB and c-Rel in control animals. We conclude that vitamin D-regulatedrelB transcription in DCs is controlled by chromatin remodeling by means of recruitment of complexes including HDAC3.