Constitutive activity of the murine IL-1 β promoter is regulated by a transcriptional repressor

Abstract

Constitutive expression of IL-1 β is kept under tight control in healthy tissues. So far no repressor elements down-regulating expression of the IL-1 β 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 β promoter activity. Further deletion analysis confirmed that the −306/−292 bp element possessed repressor activity. A putative NF- κB binding site and an AATATT palindromic sequence were identified within the 306/−292 bp element. Notably, no binding of NF- κB was observed in gel shift assays, suggesting that another nuclear activity binding to the 14 bp sequence suppressed NF- κB binding. Further, the results of gel shift assays demonstrated that the AATATT palindromic sequence, which lies immediately downstream of the putative NF- κB site, may be responsible, in conjunction with the NF- κB site, for constitutive suppression of the IL-1 β promoter. Thus, our results suggest that a novel repressor element may play a potentially important role in suppressing constitutive activity of the IL-1 β promoter.