GSE134848 Role of NuRD subunits CHD3 and CHD4 in human melanoma cells (ChIP-seq)

Contributors : Sebastien Coassolo ; Guillaume Davidson ; Luc Negroni ; Giovanni Gambi ; Sylvain Daujat ; Christophe Romier ; Irwin DavidsonSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensThe Nuclesome Remodelling and Deacetylation (NuRD) complex is an epigenetic regulator of gene expression comprising two mutually exclusive ATPase subunits CHD3 or CHD4. Here we show that CHD4 silencing in multiple types of cancer cells de-represses expression of the PADI1 (Protein Arginine Deiminase 1) and PADI3 enzymes that convert arginine to citrulline. Increased PADI1 and PADI3 expression enhances citrullination of three arginines of the key glycolytic regulatory enzyme PKM2 (pyruvate kinase) promoting excessive glycolysis, lowered ATP levels and slowed proliferation. PKM2 citrullination lowers its sensitivity to the allosteric inhibitors Tryptophan and Phenylalanine shifting equilibrium towards the allosteric activator Serine, thereby bypassing the normal physiological regulation of glycolysis by low Serine levels. Our results describe a novel pathway linking epigenetic regulation of PADI1 and PAD3 expression by CHD4 to glycolytic flux and the control of cancer cell growth.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research