Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetyltransferases*
-
Animals
-
Base Sequence
-
CCAAT-Enhancer-Binding Proteins
-
Cell Line
-
Chickens
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / physiology
-
Fibroblasts / metabolism
-
Gene Expression Regulation / physiology
-
Genes / physiology
-
Hematopoiesis / 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
-
Transfection
Substances
-
CCAAT-Enhancer-Binding Proteins
-
DNA-Binding Proteins
-
Nuclear Proteins
-
Proteins
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-myb
-
RNA, Messenger
-
Transcription Factors
-
nuclear factor NF-M
-
Poly A
-
RNA
-
Acetyltransferases
-
mim-1 protein, Gallus gallus
-
Muramidase