Epigenetic dynamics in normal and malignant B cells: die a hero or live to become a villain

Normal B cell development, activation, and terminal differentiation depend on the intricate dynamics of cooperating epigenetic and non-coding components to control the level and timing of expression of thousands of genes. Recent genome-wide studies have integratively mapped changes in the chromatin landscape, DNA methylome, 3-dimensional interactome, and coding and non-coding transcriptomes of normal and malignant B cells. Genetic ablation in human cells and mouse models has begun to elucidate the coordinated roles of essential epigenetic modifiers, key transcription factors, and long non-coding RNAs in B cell biology. Perturbation of these stewards of the epigenome drive B cell oncogenesis, but may be exploited to develop new avenues of therapy.