Role of Myc in mammalian terminal erythroid maturation

Abstract

Terminal differentiation of mammalian erythroid progenitors involves 4?5 cell divisions and induction of many erythroid important genes, followed by nuclear condensation and enucleation. The protein levels of c-myc (Myc) are reduced dramatically during late stage erythroid maturation, coinciding with cell cycle arrest in G1-phase and enucleation, suggesting possible roles for Myc in either or both of these processes. Here we demonstrate that ectopic Myc expression affects terminal erythroid maturation in a dose-dependent manner. Expression of Myc at physiological levels did not affect erythroid differentiation or cell cycle shutdown, but specifically blocked erythroid nuclear condensation and enucleation in late stage erythroblasts. Continued Myc expression prevented deacetylation of several lysine residues in histones H3 and H4 that are normally deacetylated during erythroid maturation. When over-expressed at levels higher than the physiological range, Myc promoted continued proliferation of erythroblasts at the expense of differentiation. Our study reveals an important dose-dependent function of Myc in regulating terminal maturation in mammalian erythroid cells.