Promoter-Specific Hypomethylation Correlates with IL-1 beta Overexpression in Tuberous Sclerosis Complex (TSC)
Abstract
In tuberous sclerosis complex (TSC), overexpression of numerous genes associated with inflammation has been observed. Among different proinflammatory cytokines, interleukin-1 beta (IL-1 beta) has been shown to be significantly involved in epileptogenesis and maintenance of seizures.
Recent evidence indicates that IL-1 beta gene expression can be regulated by DNA methylation of its promoter. In the present study, we hypothesized that hypomethylation in the promoter region of the IL-1 beta gene may underlie its overexpression observed in TSC brain tissue.
Bisulfite sequencing was used to study the methylation status of the promoter region of the IL-1 beta gene in TSC and control samples. We identified hypomethylation in the promoter region of the IL-1 beta gene in TSC samples.
IL-1 beta is overexpressed in tubers, and gene expression is correlated with promoter hypomethylation at CpG and non-CpG sites. Our results provide the first evidence of epigenetic modulation of the IL-1 beta signaling in TSC.
Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1 beta-mediated inflammatory signaling in TSC brain.