PAQR3 modulates H3K4 trimethylation by spatial modulation of the regulatory subunits of COMPASS-like complexes in mammalian cells

We report here a new mode of spatial regulation of H3K4 methyltransferase complexes. PAQR3, a tumor suppressor specifically localized in the Golgi apparatus, negatively regulates H3K4 trimethylation (H3K4me3) in mammalian cells. Consistently, HOXC8 and HOXA9 gene expression was negatively regulated by PAQR3 expression levels. Hypoxia-induced H3K4me3 was augmented by PAQR3 knockdown and suppressed by PAQR3 overexpression in AGS gastric cancer cells. PAQR3 was able to interact directly or indirectly with the four members of the WRAD sub-complex and tether them to the Golgi apparatus, accompanied by reduction of histone methyltransferase activity in the nucleus. PAQR3 also interfered with the interaction of WDR5 with the C-terminus of MLL1. Collectively, our study indicates that PAQR3 negatively modulates H3K4 methylation via altering the subcellular compartmentalization of the core regulatory subunits of the COMPASS-like complexes in mammalian cells.

Source: BJ Signal - February 23, 2015 Category: Biochemistry Authors: C Liu, Y Zhang, Y Hou, L Shen, Y Li, W Guo, D Xu, G Liu, Z Zhao, K Man, Y Pan, Z Wang, Y Chen Tags: BJ Signal Source Type: research