MRGBP promotes AR-mediated transactivation of KLK3 and TMPRSS2 via acetylation of histone H2A.Z in prostate cancer cells.

The androgen receptor (AR) promotes growth of prostate cancer cells by controlling the expression of target genes. This study showed that MRG domain binding protein (MRGBP) accelerated AR-mediated transactivation. We first showed that MRGBP promoted growth of AR-positive prostate cancer cells. MRGBP increased the expression of certain AR target genes, including KLK3 and TMPRSS2, and it associated with AR binding regions of these genes during androgen treatment. Furthermore, MRGBP interacted with MRG15 and TIP60 in prostate cancer cells. Androgen-stimulated AR enhanced histone H3K4me1 or H3K4me3 levels at AR binding regions. MRGBP was recruited to active gene regions through its binding with H3K4me1/3 by MRG15. Then, MRGBP promoted recruitment of TIP60 and acetylation of histone variant H2A.Z at the location of AR binding. Accordingly, AR occupancy of the AR binding regions was increased by MRGBP. Together, these results suggest that MRGBP promotes activation of AR-associated enhancer and promoter regions through an epigenetic mechanism.