Commitment to Terminal Differentiation and the Cell Cycle

Abstract

Publisher Summary Murine erythroleukemia cells are virus-transformed erythroid precursor cells that have a low probability of expressing terminal erythroid differentiation. A variety of substances, for example, dimethyl sulfoxide, hexamethylene bisacetamide, butyrate, and actinomycin D (3), markedly increase the probability of commitment toward terminal cell division and expression of erythroid characteristics, for example, accumulation of α- and β-globin mRNA. This chapter discusses factors required to express terminal erythroid differentiation. There is a requirement for DNA synthesis. Specifically, an effect of inducer early in the S phase is necessary for subsequent increased expression of globin genes. Further, in these cells, α- and β-globin structural genes are enriched in the portion of DNA replicating early in the S phase. Inducer-mediated commitment to terminal erythroid differentiation involves several steps. One or more of these steps is responsible for the acquired memory for exposure to inducer; this memory decays with a measurable half-life and is insensitive to dexamethasone and to 12-O-tetradecanoylphorbol-13-acetate as well.