Concerted action of histone methyltransferases G9a and PRMT-1 regulates PGC-1α-RIG-I axis in IFNγ treated glioma cells. (January 2017)

• Record Type: Journal Article
• Authors: Ghildiyal, Ruchi; Sen, Ellora
• Is Part Of: Cytokine. Volume 89(2017)
• Page Start: 185
• Page End: 193
• Publication Date: 2017-01
• Subjects: IFNγ interferon gamma -- RIG-I retinoic acid (RA)-inducible gene-I -- SFM serum free media -- ChIP chromatin immunoprecipitation -- NFκB nuclear factor kappa B -- PGC-1α peroxisome proliferator-activated receptor gamma coactivator-1 alpha -- PRMT-1 protein arginine methyltransferase 1 -- MTS 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling; IFNγ -- RIG-I -- G9a -- NFκB -- PGC-1α; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.12.008
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Sp-1 and NFκB serves as negative regulator of RIG-I in IFNγ treated glioma cells. IFNγ decreases occupancy of Sp1 and NFκB on RIG-1 promoter. RIG-I inhibition increases expression of de-differentiation markers. IFNγ induced PGC-1α regulates RIG-I expression. Histone methyltransferases G9a and PRMT-1 effect RIG-I and PGC-1α expression oppositely. 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.