title: 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.
authors.affiliation: National Brain Research Centre, Manesar 122 051, Haryana, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Ghildiyal
authors.affiliation: National Brain Research Centre, Manesar 122 051, Haryana, India. Electronic address: ellora@nbrc.ac.in.
authors.forename: Ellora
authors.initials: E
authors.lastname: Sen
mesh_terms: D054337:Cell Dedifferentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58 / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements
chemical_list: D006649:Histocompatibility Antigens; C573415:IFNG protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011971:Receptors, Immunologic; D012097:Repressor Proteins; D007371:Interferon-gamma; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58
keywords: G9a; IFNγ; NFκB; PGC-1α; RIG-I