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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10328128" target="_blank" >RIV/00064203:_____/16:10328128 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/16:10328128

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s12031-016-0750-7" target="_blank" >http://dx.doi.org/10.1007/s12031-016-0750-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12031-016-0750-7" target="_blank" >10.1007/s12031-016-0750-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

—

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Molecular Neuroscience

ISSN

0895-8696

e-ISSN

—

Svazek periodika

59

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

464-470

Kód UT WoS článku

000381161500004

EID výsledku v databázi Scopus

2-s2.0-84982835434