Constitutive activity of the murine IL-1 beta promoter is regulated by a transcriptional repressor.
Constitutive expression of IL-1 beta is kept under tight control in healthy tissues. So far no repressor elements down-regulating expression of the IL-1 beta gene have been described. In the current study, a deletion analysis approach was utilized to identify a region spanning -306/-292 bp upstream of the transcription start site, which appeared to down-regulate constitutive IL-1 beta promoter activity. Further deletion analysis confirmed that the -306/-292 bp element possessed repressor activity. A putative NF-kappaB binding site and an AATATT palindromic sequence were identified within the 306/-292 bp element. Notably, no binding of NF-kappaB was observed in gel shift assays, suggesting that another nuclear activity binding to the 14 bp sequence suppressed NF-kappaB binding. Further, the results of gel shift assays demonstrated that the AATATT palindromic sequence, which lies immediately downstream of the putative NF-kappaB site, may be responsible, in conjunction with the NF-kappaB site, for constitutive suppression of the IL-1 beta promoter. Thus, our results suggest that a novel repressor element may play a potentially important role in suppressing constitutive activity of the IL-1 beta promoter.
Lebedeva
T V
TV
New England Medical Center, Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.
Singh
A K
AK
D000818:Animals; D001665:Binding Sites; D015536:Down-Regulation; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000235:genetics*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D007375:Interleukin-1; D016328:NF-kappa B; D012097:Repressor Proteins; D014157:Transcription Factors