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RNA polymerase II inhibitor, 5,6‐dichloro‐1‐β‐D‐ribofuranosylbenzimidazole (DRB) causes erythroleukemic differentiation and transcriptional activation of erythroid genes
Author(s) -
Hensold Jack O.,
Barth Diane,
Stratton Carl A.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199607)168:1<105::aid-jcp13>3.0.co;2-6
Subject(s) - biology , cellular differentiation , gene , gene expression , transcription (linguistics) , inducer , microbiology and biotechnology , phenotype , regulation of gene expression , genetics , linguistics , philosophy
Friend virus‐transformed murine erythroleukemia (MEL) cells are a useful system for studying the regulation of erythroid growth and differentiation. As a manifestation of the leukemic process, these erythroblasts 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 mechanisms 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, induces differentiation of these cells, including the transcriptional activation of erythroid genes. The effects of DRB on nonerythroid gene expression 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 expression in MEL cells while having differing effects on nonerythroid gene expression and on cell growth suggests that expression of the terminally differentiated phenotype represents a common pathway that can be triggered by different mechanisms. © 1996 Wiley‐Liss, Inc.