Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation

K. Todokoro, R. J. Watson, H. Higo, H. Amanuma, S. Kuramochi, H. Yanagisawa, Y. Ikawa

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The role of nuclear protooncogenes during erythroid cell differentiation was examined by transfecting exogenous c-fos and c-myb genes into mouse erythroleukemia cells, which can be induced to differentiate either with erythropoietin (Epo) or dimethyl sulfoxide. Expression of exogenous c-myb or c-fos oncogene completely inhibited Epo-induced erythroid differentiation but only partially inhibited dimethyl sulfoxide-induced differentiation. Normally Epo-induced differentiation leads to drastic decline of c-myb mRNA levels and an increase of c-myc transcripts in the early stage of differentiation. Cells expressing exogenous c-fos gene, however, maintained high levels of c-myb mRNA after Epo treatment. This high level of c-myb transcripts was found to be due to block of transcription shutoff (or transcriptional activation) rather than to mRNA stabilization. It is concluded that the down-regulation of endogenous c-myb gene expression is a prerequisite for commitment of Epo-induced erythroid differentiation and that expression of c-myb gene may be indirectly regulated by c-fos gene product. We also concluded that early down-regulation of c-myc gene expression is not essential for erythroid differentiation and that gene regulation of chemically induced erythroid differentiation may differ from that of Epo-induced differentiation.

Original languageEnglish (US)
Pages (from-to)8900-8904
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - 1988

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