Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types.
The c-Myb transcription factor regulates the differentiation of immature erythroid, lymphoid, and myeloid cells, although only the latter cells become transformed by the v-myb oncogene. These are also the only cells that express the Myb-regulated gene mim-1, suggesting that Myb requires tissue-specific, cooperating factors to activate such genes. Here, we investigated the tissue-specific regulation of the mim-1 promoter and found that it not only contains binding sites for Myb but also for NF-M, a myeloid-specific transcription factor that probably corresponds to mammalian C/EBP beta. Both types of binding sites were found to be required for full activity of the promoter. Remarkably, ectopic coexpression of Myb and NF-M proteins in erythroid cells or fibroblasts was sufficient to induce endogenous markers of myeloid differentiation, like the mim-1 and lysozyme genes. Our results indicate that c-Myb and NF-M proteins act as a bipartite, combinatorial signal that regulates the expression of myeloid-specific genes, even in heterologous cell types.
Ness
S A
SA
Zentrum für Molekulare Biologie, Universität Heidelberg (ZMBH), Germany.
Kowenz-Leutz
E
E
Casini
T
T
Graf
T
T
Leutz
A
A
D000123:Acetyltransferases; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005796:Genes / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics; D008969:Molecular Sequence Data; D009113:Muramidase / Q000096:biosynthesis / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D011061:Poly A / Q000032:analysis / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb; D011784:Quail; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012333:RNA, Messenger; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D014157:Transcription Factors; C075191:nuclear factor NF-M; D011061:Poly A; D012313:RNA; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus; D009113:Muramidase