Coordination of erythropoiesis by the transcription factor c-Myb.
The involvement of the transcription factor c-Myb in promoting the proliferation and inhibition of erythroid cell differentiation has been established in leukemia cell models. The anemia phenotype observed in c-myb knockout and knockdown mice highlights a critical role for c-Myb in erythropoiesis. However, determining the reason for the failure of erythropoiesis in these mice and the precise function of c-Myb in erythroid progenitors remains elusive. We examined erythroid development under conditions of reduced c-Myb protein levels and report an unexpected role for c-Myb in the promotion of commitment to the erythroid lineage and progression to erythroblast stages. c-myb knockdown erythroid colony-forming unit (CFU-E) stage progenitors displayed an immature phenotype and aberrant expression of several hematopoietic regulators. To extend our findings, we analyzed the response of normal enriched erythroid progenitors to inducible disruption of a floxed c-myb allele. In agreement with the c-myb knockdown phenotype, we show that c-Myb is strictly required for expression of the c-Kit receptor in erythroid cells.
Institute of Biomedical Research, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Alexandros
A
Vegiopoulos
Paloma
P
García
Nikla
N
Emambokus
Jon
J
Frampton
D000740:Anemia / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D004900:Erythroblasts / Q000166:cytology / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D020598:Proto-Oncogene Proteins c-myb / Q000172:deficiency / Q000378:metabolism
D020598:Proto-Oncogene Proteins c-myb; D019009:Proto-Oncogene Proteins c-kit