Nuclear Opening and Histone Release in Mammalian Terminal Erythropoiesis

Type of Award: Catalyst
Date Awarded: March 2015
Award End Date: February 2017
Amount Awarded: $ 200,000.00
PI(s): Peng Ji, MD, PhD, NU; Amittha Wickrema, PhD, UChicago;

Abstract: Mammalian red blood cell development involves a dramatic nuclear condensation that is essential for differentiation. However, the mechanism of nuclear condensation is poorly understood. In an effort to fully understand the mechanism of nuclear condensation, we studied nuclear condensation in a temporal fashion using a mouse erythropoiesis model and discovered the presence of a unique nuclear opening from which major histones, except one type of histones, H2AZ, are released out of the nucleus. Based on these novel observations we hypothesize that caspase-3-mediated regulation, and direct involvement of H2AZ in histone replacement and nuclear release are responsible for chromatin condensation during mouse and human red blood cell development. Successful accomplishment of the proposed research will reveal a novel facet of red blood cell development, which could provide critical insights in the pathogenesis of certain red cell diseases with defective nuclear condensation and/or terminal differentiation.