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

Research output: Contribution to journalArticle

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Abstract

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
Volume85
Issue number23
StatePublished - 1988

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myb Genes
Erythropoietin
Down-Regulation
Gene Expression
fos Genes
Dimethyl Sulfoxide
Messenger RNA
Transcriptional Activation
Leukemia, Erythroblastic, Acute
Erythroid Cells
myc Genes
Oncogenes
Cell Differentiation
Genes

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation. / Todokoro, K.; Watson, R. J.; Higo, H.; Amanuma, H.; Kuramochi, S.; Yanagisawa, H.; Ikawa, Y.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 85, No. 23, 1988, p. 8900-8904.

Research output: Contribution to journalArticle

Todokoro, K, Watson, RJ, Higo, H, Amanuma, H, Kuramochi, S, Yanagisawa, H & Ikawa, Y 1988, 'Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation', Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 23, pp. 8900-8904.
Todokoro, K. ; Watson, R. J. ; Higo, H. ; Amanuma, H. ; Kuramochi, S. ; Yanagisawa, H. ; Ikawa, Y. / Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation. In: Proceedings of the National Academy of Sciences of the United States of America. 1988 ; Vol. 85, No. 23. pp. 8900-8904.
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AU - Todokoro, K.

AU - Watson, R. J.

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AU - Amanuma, H.

AU - Kuramochi, S.

AU - Yanagisawa, H.

AU - Ikawa, Y.

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N2 - 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.

AB - 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.

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