AR signaling mediates transrepression of the NR5A2 gene (IMAGE)
Caption
(A, B) Luciferase reporter assay of regulatory regions of the NR5A2 gene performed in AR-positive VCaP cells. (A) Left panel: Schematic diagram shows the five reporter constructs driven by different ARBS-containing DNA fragments derived from the enhancers, promoter and intron 1 of NR5A2. Right panel: The results showed that the luciferase activities of the ARBS3 and ARBS-promoter reporters were significantly repressed, while those of the ARBS2 and ARBS-intron1 reporters were moderately/slightly repressed by DHT treatment. (B) Left panel: Schematic diagram shows two mutant reporters with truncations of ARBS-binding motifs. Right panel: The results showed that deletions of ARBSs in ARBS3 and ARBS-promoter reporters abolished their DHT-induced luciferase activities. (C) Schematic diagram shows the proposed model of the androgen-induced dynamic conformational change in chromatin looping within the NR5A2 TAD. Upon DHT treatment, a new chromatin loop is formed by the interaction between ARBS3 and the promoter of NR5A2, with the recruitment of other corepressors or epigenetic modifiers, including ERG, EZH2 and HDACs, which may favor the suppression on the NR5A2 transcription. ∗P < 0.05; ∗∗P < 0.01; ns: not significant.
Credit
Wenxing You, Tiantian Gao, Haolong Li, Daniel Hau Tak Lam, Wenjuan Xie, Lijia Xiao, Weijie Gao, Dinglan Wu, Junjian Wang, Yuliang Wang, Franky Leung Chan
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