Authors: Fuso A., Iyer A.M., van Scheppingen J., Maccarrone M., Scholl T., Hainfeller J.A., Feucht M., Jansen F.E., Spliet W.G., Krsek P., Zamecnik J., Mühlebner A., Aronica E.

J Mol Neurosci. 2016 Aug;59(4): 464-70. doi: 10.1007/s12031-016-0750-7. Epub 2016 Apr 28.


In tuberous sclerosis complex (TSC), overexpression of numerous genes associated with inflammation has been observed. Among different proinflammatory cytokines, interleukin-1B (IL-1B) has been shown to be significantly involved in epileptogenesis and maintenance of seizures. Recent evidence indicates that IL-1B 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-1B 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-1B gene in TSC and control samples. IL-1B 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-1B signaling in TSC. Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1B-mediated inflammatory signaling in TSC brain.