Epigenetic regulation of hematopoiesis.

Epigenetic regulation is required not only for development, but also for tissue homeostasis, which is maintained via the self-renewal and differentiation of somatic stem cells. Accumulating evidence suggests that epigenetic regulators play critical roles in the maintenance of both self-renewing hematopoietic stem cells and leukemic stem cells. Recent genome-wide comprehensive analyses have identified mutations in epigenetic regulator genes, including genes whose products modify DNA and histones in hematological malignancies. Among these epigenetic regulators, repressive histone modifications by Polycomb-group complexes have been most fully characterized in hematopoietic stem cells, and are recognized as general regulators of stem cells. Hematopoietic stem cells are controlled by both cell-intrinsic and -extrinsic regulators, including transcription factors, signal transduction pathways, and niche factors. However, there is little insight into the mechanism of how epigenetic regulators act in concert with these factors to ensure blood homeostasis. In this review, we highlight recent findings in epigenetic regulation of hematopoiesis with emphasis on the role of Polycomb-group proteins and DNA-methylation modulators in hematopoietic stem cells and their progeny.