Promoter-Specific Hypomethylation Correlates with IL-1[beta] Overexpression in Tuberous Sclerosis Complex (TSC)

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 evidenc...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2016-08, Vol.59 (4), p.464
Main Authors: Fuso, A, Iyer, A M, van Scheppingen, J, Maccarrone, M, Scholl, T, Hainfellner, J A, Feucht, M, Jansen, F E, Spliet, W G, Krsek, P, Zamecnik, J, Mühlebner, A, Aronica, E
Format: Article
Language:English
Subjects:
Antibodies
Autopsies
Brain research
Convulsions & seizures
Cytokines
DNA methylation
Epigenetics
Gene expression
Hospitals
Localization
Neurology
Pathology
Pediatrics
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Summary: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.
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-016-0750-7