An inability to properly sustain blood cell production results in the development of hematopoietic disorders. Epigenetic regulators have been shown to be involved in the function of hematopoietic stem and progenitor cells; however, dysfunction of these enzymes is associated with development of malignancies. In this episode Stephen Nimer and colleagues identify the type II arginine methyltransferase PRMT5 as an important regulator of adult hematopoiesis. Mice lacking PRMT5 developed fatal pancytopenia due to reduced proliferation of hematopoietic progenitor cells as the results of impaired cytokine signaling and increased p53 signaling. Hematopoietic stem cell populations were not initially reduced in these animals; however, this population was unable to restore blood cell populations in lethally irradiated mice. Together, the results of this study provide important insight into the role of PRMT5-mediated gene expression in maintaining hematopoietic homeostasis.
Epigenetic regulators play critical roles in normal hematopoiesis, and the activity of these enzymes is frequently altered in hematopoietic cancers. The major type II protein arginine methyltransferase PRMT5 catalyzes the formation of symmetric dimethyl arginine and has been implicated in various cellular processes, including pluripotency and tumorigenesis. Here, we generated
Fan Liu, Guoyan Cheng, Pierre-Jacques Hamard, Sarah Greenblatt, Lan Wang, Na Man, Fabiana Perna, Haiming Xu, Madhavi Tadi, Luisa Luciani, Stephen D. Nimer