The gene for the transcription factor BHLHE40/DEC1/stra13 is a dynamically regulated primary target of the vitamin D receptor

Abstract

The basic helix-loop-helix protein BHLHE40 functions as a transcriptional repressor and is involved in the control of cellular growth, development and circadian rhythms. By the use of genome-wide data on vitamin D receptor (VDR) location, open chromatin and histone modification backed-up by gene-specific mRNA expression studies we show that the human BHLHE40 gene is dynamically up-regulated by the VDR ligand 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) and down-regulated by the histone deactylase inhibitor trichostatin A. The VDR binding site is located 1.7kb upstream of the transcription start site of the BHLHE40 gene and the chromatin at this genomic site is significantly opened by treatment with 1α,25(OH)2D3. The stair case style fluctuations in the BHLHE40 mRNA accumulation relate to the short half-life of the gene's mRNA of 0.9h. The identification of the widely expressed BHLHE40 gene as a primary VDR target may explain secondary effects of 1α,25(OH)2D3 on BHLHE40 responding genes. This article is part of a Special Issue entitled 'Vitamin D Workshop'.