title: C/EBP gamma has a stimulatory role on the IL-6 and IL-8 promoters.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824-4320, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
authors.forename: Sara
authors.initials: S
authors.lastname: Parkin
authors.forename: Peter F
authors.initials: PF
authors.lastname: Johnson
authors.forename: Richard C
authors.initials: RC
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D017930:Genes, Reporter; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D016350:Leucine Zippers; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020033:Protein Isoforms; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha