Promoter-Specific Hypomethylation Correlates with IL-1? 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? (IL-1?) has been shown to be significantly involved in epileptogenesis and maintenance of seizures. Recent evidence indicates that IL-1? 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? 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? gene in TSC and control samples. We identified hypomethylation in the promoter region of the IL-1? gene in TSC samples. IL-1? 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? signaling in TSC. Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1?-mediated inflammatory signaling in TSC brain.

SUBMITTER: Fuso A 

PROVIDER: S-EPMC4972849 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature