RNA-POLYMERASE-II INHIBITOR, 5,6-DICHLORO-1-BETA-D-RIBOFURANOSYLBENZIMIDAZOLE (DRB) CAUSES ERYTHROLEUKEMIC DIFFERENTIATION AND TRANSCRIPTIONAL ACTIVATION OF ERYTHROID GENES

Friend virus-transformed murine erythroleukemia (MEL) cells are a usef ul system for studying the regulation of erythroid growth and differen tiation. As a manifestation of the leukemic process, these erythroblas ts are blocked in their ability to terminally differentiate. However, this block is reversible as a variety of different agents are capable of inducing differentiation of these malignant erythroblasts. The mech anisms by which these agents cause differentiation remains unknown. We report here that 5,6-dichlorobenzimidazole (DRB), which inhibits RNA polymerase II by causing premature termination of transcription, induc es differentiation of these cells, including the transcriptional activ ation of erythroid genes. The effects of DRB on nonerythroid gene expr ession and on cell growth are substantially different than that of the commonly used inducer, dimethyl sulfoxide (DMSO). The shared ability of DMSO, DRB, and other unrelated agents to induce erythroid gene expr ession in MEL cells while having differing effects on nonerythroid gen e expression and on cell growth suggests that expression of the termin ally differentiated phenotype represents a common pathway that can be triggered by different mechanisms. (C) 1996 Wiley-Liss, Inc.*