Circadian rhythmicity: A functional connection between differentiated embryonic chondrocyte-1 (DEC1) and small heterodimer partner (SHP)

Abstract

Circadian rhythm misalignment has been increasingly recognized to pose health risk for a wide range of diseases, particularly metabolic disorders. The liver maintains metabolic homeostasis and expresses many circadian genes, such as differentiated embryo chondrocyte-1 (DEC1) and small heterodimer partner (SHP). DEC1 is established to repress transcription through E-box elements, and SHP belongs to the superfamily of nuclear receptors and has multiple E-box elements in its promoter. Importantly, DEC1 and SHP are inversely oscillated. This study was performed to test the hypothesis that the SHP gene is a target gene of DEC1. Cotransfection demonstrated that DEC1 repressed the SHP promoter and attenuated the transactivation of the classic circadian activator complex of Clock/Bmal1. Site-directed mutagenesis, electrophoretic mobility shift assay and chromatin immunoprecipitation established that the repression was achieved through the E-box in the proximal promoter. Transfection of DEC1 suppressed the expression of SHP. In circadian-inducing cells, the epileptic agent valproate inversely altered the expression of DEC1 and SHP. Both DEC1 and SHP are involved in energy balance and valproate is known to induce hepatic steatosis. Our findings collectively establish that DEC1 participates in the negative loop of SHP oscillating expression with potential implications in metabolic homeostasis.

Dechlorination and demethylation of ochratoxin A enhance blocking activity of PXR activation, suppress PXR expression and reduce cytotoxicity

“…The chemiluminescent signal was captured by Carestream 2200 PRO Imager (Shi et al, 2011). The immunofluorescence staining was performed as described previously (Marczak and Yan, 2017). hPXR-HRE cells were seeded in chamber slides at 40-80% confluence and cultured overnight.…”

Overcoming ABCB1-mediated multidrug resistance by transcription factor BHLHE40

“…Basic helix-loop-helix (BHLH) family member e40, also known as differentiated embryonic chondrocytes-expressed gene 1 (DEC1), is a transcription repressor directly binding to the promoters and/or enhancer regions of the target genes [12] , [13] , [14] . Its effects are also ascribed to indirect regulation of gene expression by interacting with RNA polymerase II, other transcription factors or histone modifiers [15] .…”

Cisplatin increases carboxylesterases through increasing PXR mediated by the decrease of DEC1

“…Human differentiated embryonic chondrocyte-expressed gene 1 (DEC1), also named mouse stimulated with retinoic acid 13 (STRA13), and rat split and hairy-related protein (SHARP), is one of the basic helix-loop-helix transcriptional factors. It is correlated with cell differentiation, proliferation, biological rhythm and homeostasis of metabolism [ 15 – 16 ] . DEC1 can be combined with retinoid X receptor alpha (RXRα), which impedes the formation of heterodimer of RXR and other nuclear receptors, such as PXR that leads to the repression of PXR function [ 17 ] .…”