Ness S A, Kowenz-Leutz E, Casini T, Graf T, Leutz A
Zentrum für Molekulare Biologie, Universität Heidelberg (ZMBH), Germany.
Genes Dev. 1993 May;7(5):749-59. doi: 10.1101/gad.7.5.749.
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.
c-Myb转录因子调节未成熟红细胞、淋巴细胞和髓细胞的分化，尽管只有后者细胞会被v-myb癌基因转化。这些也是唯一表达Myb调节基因mim-1的细胞，这表明Myb需要组织特异性的协同因子来激活此类基因。在这里，我们研究了mim-1启动子的组织特异性调节，发现它不仅含有Myb的结合位点，还含有NF-M的结合位点，NF-M是一种髓细胞特异性转录因子，可能对应于哺乳动物的C/EBPβ。发现这两种类型的结合位点对于启动子的完全活性都是必需的。值得注意的是，在红细胞或成纤维细胞中异位共表达Myb和NF-M蛋白足以诱导髓细胞分化的内源性标志物，如mim-1和溶菌酶基因。我们的结果表明，c-Myb和NF-M蛋白作为一种二元组合信号，即使在异源细胞类型中也能调节髓细胞特异性基因的表达。
