Modulation of gene expression during terminal cell differentiation: murine erythroleukemia.

MELC are virus-transformed cells capable of indefinite proliferation that are blocked in differentiation at an early erythroid precursor stage, probably corresponding to CFU-e. A variety of agents, among them HMBA and Me2SO, induce MELC to terminal differentiation and expression of characteristics similar to that associated with normal erythropoiesis. During inducer-mediated terminal differentiation, modulation of expression of a number of genes occurs. Studies to date have characterized inducer-mediated alterations in chromatin structure associated with activation of alpha and beta maj globin genes. Inducer-mediated MELC terminal cell division is also associated with a decrease in the synthesis of the nuclear protein p53, a protein that has been implicated as a requirement for the progression from G1 to S in the cell cycle. HMBA-mediated commitment to terminal cell division is suppressed by steroid. HMBA induces accumulation of mRNAs that may be required for commitment to terminal cell division and whose translation is suppressed by dexamethasone. At least two inducer-activated genes have been identified that may play a role in the transition of terminal cell division.