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

Genes Dev. 1993 May;7(5):749-59. doi: 10.1101/gad.7.5.749.

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