The v-Myb oncoprotein activates C/EBPbeta expression by stimulating an autoregulatory loop at the C/EBPbeta promoter

Biochim Biophys Acta. 1999 Oct 28;1447(2-3):175-84. doi: 10.1016/s0167-4781(99)00168-2.

Abstract

Previous studies have implicated the CCAAT box/enhancer binding protein beta (C/EBPbeta) in the regulation of cell-type specific gene expression in myelomonocytic cells and in the activation of target genes by the transcription factor v-Myb. To better understand the role of C/EBPbeta in myelomonocytic cells we have cloned the chicken C/EBPbeta gene and studied its regulation. The chicken C/EBPbeta promoter contains a number of C/EBP binding sites and is activated by C/EBPbeta, suggesting that the C/EBPbeta gene is autoregulated by its own protein product. Interestingly, the C/EBPbeta promoter is not activated by C/EBPalpha, another C/EBP family member highly expressed in myelomonocytic cells, indicating that the autoregulation is specific for C/EBPbeta. Comparison of different C/EBP inducible promoters shows that the relative transactivation potential of C/EBPalpha and beta is extremely dependent on the promoter context. By using the promoters of the mim-1 and C/EBPbeta genes and by exchanging the DNA-binding domains between C/EBPalpha and beta we show that the observed promoter preferences of C/EBPalpha and beta are not due to differential DNA-binding but instead depend on the transactivation domains of these proteins. The C/EBPbeta promoter also contains several Myb binding motifs, suggesting that the C/EBPbeta gene is also myb-inducible. We show that the C/EBPbeta promoter is activated synergistically by v-Myb and C/EBPbeta and that transcription of the endogenous C/EBPbeta gene is increased by v-Myb. Thus, our results identify the C/EBPbeta gene as a novel v-Myb target gene. Taken together, our data suggest a model for the regulation of C/EBPbeta expression in which v-Myb stimulates the synthesis of C/EBPbeta by enhancing an autoregulatory loop acting on the C/EBPbeta promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication / genetics
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • Chickens
  • Cloning, Molecular
  • Coturnix
  • DNA-Binding Proteins / genetics*
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation*
  • Genes, myb*
  • Molecular Sequence Data
  • Monocytes / physiology*
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic / genetics

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins

Associated data

  • GENBANK/AF178567