Cells of the immune system are generated from multipotent haematopoietic stem cells (HSCs) through an elaborated process of differentiation. Self-renewal of the HSC and a tightly controlled differentiation are therefore vital to replenish the blood and immune system throughout the lifespan of an organism. HSCs proliferation, as well as the successive stages of differentiation into more committed progenitors, are regulated at the transcriptional level through epigenetic modifications. These modifications include DNA methylation, histone modifications (such as acetylation, methylation, phosphorylation, SUMOylation and ubiquitylation) and chromatin remodeling. The enzymes responsible for these chromatin modifications are therefore critical for normal blood and immune system homeostasis. The finding that these chromatin modifiers are common targets of mutations or translocations in leukaemia further highlights their functional requirements. © 2013 The Paterson Institute for Cancer Research Immunology © 2013 Blackwell Publishing Ltd.