Promoter-Specific Hypomethylation Correlates with IL-1β Overexpression in Tuberous Sclerosis Complex (TSC).
Promoter-Specific Hypomethylation Correlates with IL-1β Overexpression in Tuberous Sclerosis Complex (TSC).
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DOI：
10.1007/s12031-016-0750-7
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
Aronica E
中科院分区：
文献类型：
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作者：
Fuso A;Iyer AM;van Scheppingen J;Maccarrone M;Scholl T;Hainfellner JA;Feucht M;Jansen FE;Spliet WG;Krsek P;Zamecnik J;Mühlebner A;Aronica E
在结节性硬化症（TSC）中，已观察到许多与炎症相关的基因过表达。在不同的促炎细胞因子中，白细胞介素-1 β（IL-1β）已被证明显著参与癫痫的发生和癫痫发作的维持。近年来的研究表明，IL-1β基因启动子区的甲基化可以调控IL-1β的表达。在本研究中，我们假设IL-1β基因启动子区的低甲基化可能是其在TSC脑组织中观察到的过表达的基础。亚硫酸氢盐测序用于研究TSC和对照样品中IL-1β基因启动子区的甲基化状态。我们在TSC样品中鉴定了IL-1β基因启动子区的低甲基化。IL-1β在块茎中过表达，基因表达与启动子CpG和非CpG位点的低甲基化相关。我们的结果提供了TSC中IL-1β信号转导的表观遗传调节的第一个证据。因此，靶向表观遗传改变的策略可以提供新的治疗途径来控制TSC脑中白细胞介素-1 β介导的炎症信号传导的持续激活。
In tuberous sclerosis complex (TSC), overexpression of numerous genes associated with inflammation has been observed. Among different proinflammatory cytokines, interleukin-1β (IL-1β) has been shown to be significantly involved in epileptogenesis and maintenance of seizures. Recent evidence indicates that IL-1β 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-1β 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-1β gene in TSC and control samples. We identified hypomethylation in the promoter region of the IL-1β gene in TSC samples. IL-1β 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-1β signaling in TSC. Thus, strategies that target epigenetic alterations could offer new therapeutic avenues to control the persistent activation of interleukin-1β-mediated inflammatory signaling in TSC brain.