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C/EBP gamma has a stimulatory role on the IL-6 and IL-8 promoters.

CCAAT/enhancer-binding protein gamma (C/EBP gamma) is an ubiquitously expressed member of the C/EBP family of transcription factors that has been shown to be an inhibitor of C/EBP transcriptional activators and has been proposed to act as a buffer against C/EBP-mediated activation. We have now unexpectedly found that C/EBP gamma dramatically augments the activity of C/EBP beta in lipopolysaccharide induction of the interleukin-6 and interleukin-8 promoters in a B lymphoblast cell line. This activating role for C/EBP gamma is promoter-specific, neither being observed in the regulation of a simple C/EBP-dependent promoter nor the TNF alpha promoter. C/EBP gamma activity also shows cell-type specificity with no activity observed in a macrophage cell line. Studies with chimeric C/EBP proteins implicate the formation of a heterodimeric leucine zipper between C/EBP beta and C/EBP gamma as the critical structural feature required for C/EBP gamma stimulatory activity. These findings suggest a unique role for C/EBP gamma in B cell gene regulation and, along with our previous observation of the ability of C/EBP basic region-leucine zipper domains to confer lipopolysaccharide inducibility of interleukin-6, suggest that the C/EBP leucine zipper domain has a role in C/EBP function beyond allowing dimerization between C/EBP family members.

Pubmed ID: 12177065

Authors

  • Gao H
  • Parkin S
  • Johnson PF
  • Schwartz RC

Journal

The Journal of biological chemistry

Publication Data

October 11, 2002

Associated Grants

None

Mesh Terms

  • Animals
  • B-Lymphocytes
  • CCAAT-Enhancer-Binding Proteins
  • Cell Line
  • DNA-Binding Proteins
  • Dimerization
  • Genes, Reporter
  • Humans
  • Interleukin-6
  • Interleukin-8
  • Leucine Zippers
  • Lipopolysaccharides
  • Mice
  • NF-kappa B
  • Promoter Regions, Genetic
  • Protein Isoforms
  • Trans-Activators
  • Transcription Factor RelA
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha