A Potential Suppressive Effect of Natural Antisense IL-1 beta RNA on Lipopolysaccharide-Induced IL-1 beta Expression

作者:Lu Jiawei; Wu Xiurong; Hong Mao; Tobias Peter*; Han Jiahuai
来源:The Journal of Immunology, 2013, 190(12): 6570-6578.
DOI:10.4049/jimmunol.1102487

摘要

Although more than half of genomic loci are believed to have antisense transcription, whether antisense transcription is involved in cytokine expression has not been studied. In this study, we show that some loci of innate immunity related genes do have antisense transcripts. We investigated the effect of several antisense RNAs, including anti-4-1BBL, anti-p100, and anti-IL-1 beta, on their cognate sense gene's expression in macrophages. We found that overexpression of antisense IL-1 beta transcript suppressed IL-1 beta expression. Anti-IL-1 beta is complementary to the sequence in the 59 upstream region of the IL-1 beta promoter. Its mediated inhibition of IL-1 beta production occurred at the transcriptional level. Anti-IL-1b did not alter the methylation status of the IL-1 beta promoter. However, chromatin immunoprecipitation assays revealed that the anti-IL-1 beta transcript can change the chromatin structure of the IL-1 beta promoter by decreasing H3K4 trimethylation on the promoter, which is at least part of the mechanism underlying the reduced binding of RNA polymerase II to the IL-1 beta promoter upon anti-IL-1 beta expression. Our data suggest that some antisense transcripts of innate immunity-related genes play a role by regulating cytokine expression.