Myb and NF-M : combinatorial activators of myeloid genes in heterologous cell types

• Published in: Genes & development 1993-05, Vol.7 (5), p.749-759
• Main Authors: NESS, S. A, KOWENZ-LEUTZ, E, CASINI, T, GRAF, T, LEUTZ, A
• Format: Article
• Language: English
• Subjects: Acetyltransferases; Animals; Base Sequence; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins; Cell Line; Chickens; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; Genes - physiology; Hematopoiesis - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Muramidase - biosynthesis; Muramidase - genetics; Mutagenesis, Site-Directed; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Poly A - analysis; Poly A - isolation & purification; Polymerase Chain Reaction; Promoter Regions, Genetic; Proteins - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-myb; Quail; RNA - analysis; RNA - isolation & purification; RNA, Messenger; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transfection
• ISSN: 0890-9369; 1549-5477
• 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.