MLL and KDM5A activity during cell cycle progression depend on Ras signalling

Abstract

Cell cycle progression is regulated by many extracellular stimuli and intracellular signaling. Interaction between different epigenetic modifiers and transcription factors regulate the expression of genes encoding proteins involved in cell cycle control. Along with the cyclin-CDK complexes and phosphatases, RAS- signaling play crucial role to direct the cell passage through different stages of cell cycle. In this scenario, chromatin configuration is important for the progression of cell division and chromatin modifications (DNA methylation and histone modifications) helps to attain correct chromatin folds. Here, in this study we analyzed how modulation of H3K4me3 by MLL1 and KDM5A affect cell cycle progression. As slow and fast cycling cell lines exhibited differences in mechanisms of regulation, from in-silico screening and experimental demonstration we deciphered that the expression of the MAPK effector, RAS is involved to controlling the expression and activity of KDM5A and MLL proteins to balance H3K4me3 oscillation throughout cell cycle.