Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation.
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 a 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.
Todokoro
K
K
Tsukuba Life Science Center, Institute of Physical and Chemical Research, Ibaraki, Japan.
Watson
R J
RJ
Higo
H
H
Amanuma
H
H
Kuramochi
S
S
Yanagisawa
H
H
Ikawa
Y
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D004921:Erythropoietin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006207:Half-Life; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental; D051379:Mice; D011519:Proto-Oncogenes / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D015342:DNA Probes; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D004921:Erythropoietin