Concerted action of histone methyltransferases G9a and PRMT-1 regulates PGC-1α-RIG-I axis in IFNγ treated glioma cells

Abstract

IFNγ induced de-differentiation markers are negatively regulated by retinoic acid inducible gene (RIG-I) in glioma cells. In addition to RIG-I, IFNγ treatment increased H3K9me2; histone methyltransferases (HMTs) G9a and protein arginine methyltransferase-1 (PRMT-1) levels. While G9a inhibition further increased IFNγ induced RIG-I, PRMT-1 inhibition abrogated IFNγ elevated RIG-I levels. IFNγ induced Sp1 and NFκB served as negative regulators of RIG-I, with decreased occupancy of Sp1 and NFκB observed on the RIG-I promoter. A diminished H3K9Me2 enrichment was observed at the NFκB but not at Sp-1 binding site. IFNγ induced PPAR gamma coactivator-1 alpha (PGC-1α) positively regulated RIG-I; with PRMT-1 and G9a affecting PGC-1α in a counter-regulatory manner. These findings demonstrate how concerted action of HMTs aid PGC-1α driven RIG-I for the sustenance of glioma cells in a de-differentiated state.