CARM1 is involved in CYP1A1 gene expression as a transcriptional coactivator

Abstract

Protein arginine methyltransferases (PRMTs) have been proposed as a transcriptional coactivators in the induction of CYP1A1. In this study, we investigated the change of AhR and CYP1A1 expression by inhibition of CARM1 (also known as PRMT4) to show the involvement of protein arginine methylation in CYP1A1 gene expression. Also, we tested the hypothesis that CARM1 recruitment to the CYP1A1 promoter and subsequent histone arginine methylation are required for the activation of transcription. We found that treatment of HepG2 cells with silencing RNA targeting CARM1 or an arginine methyltransferase inhibitor (AMI-5) significantly decreased the CYP1A1 gene expression level. Furthermore, treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which increases histone arginine methylation in histone H3R17, also caused increases in CARM1 and H3R17 signals in chromatin immunoprecipitation assays. These results indicate that CARM1 is recruited to the CYP1A1 promoter region as a coactivator, and histone arginine methylation makes XRE (xenobiotic responsive element) regions more accessible for transcription.