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

A Fuso; A M Iyer; J van Scheppingen; M Maccarrone; T Scholl; J A Hainfellner; M Feucht; F E Jansen; W G Spliet; P Krsek; J Zamecnik; A Mühlebner; E Aronica

doi:10.1007/s12031-016-0750-7

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

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

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Abstract

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.

Original language	English
Pages (from-to)	464-470
Number of pages	7
Journal	Journal of molecular neuroscience
Volume	59
Issue number	4
DOIs	https://doi.org/10.1007/s12031-016-0750-7
Publication status	Published - 28 Apr 2016

Keywords

Cortical tuber
Epigenetic regulation
Inflammation
Interleukin-1β
Tuberous sclerosis complex

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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. (2016). Promoter-Specific Hypomethylation Correlates with IL-1β Overexpression in Tuberous Sclerosis Complex (TSC). Journal of molecular neuroscience, 59(4), 464-470. https://doi.org/10.1007/s12031-016-0750-7

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title = "Promoter-Specific Hypomethylation Correlates with IL-1β 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-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.",

keywords = "Cortical tuber, Epigenetic regulation, Inflammation, Interleukin-1β, Tuberous sclerosis complex",

author = "A Fuso and Iyer, {A M} and {van Scheppingen}, J and M Maccarrone and T Scholl and Hainfellner, {J A} and M Feucht and Jansen, {F E} and Spliet, {W G} and P Krsek and J Zamecnik and A M{\"u}hlebner and E Aronica",

year = "2016",

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doi = "10.1007/s12031-016-0750-7",

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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 2016, 'Promoter-Specific Hypomethylation Correlates with IL-1β Overexpression in Tuberous Sclerosis Complex (TSC)', Journal of molecular neuroscience, vol. 59, no. 4, pp. 464-470. https://doi.org/10.1007/s12031-016-0750-7

TY - JOUR

T1 - Promoter-Specific Hypomethylation Correlates with IL-1β Overexpression in Tuberous Sclerosis Complex (TSC)

AU - Fuso, A

AU - Iyer, A M

AU - van Scheppingen, J

AU - Maccarrone, M

AU - Scholl, T

AU - Hainfellner, J A

AU - Feucht, M

AU - Jansen, F E

AU - Spliet, W G

AU - Krsek, P

AU - Zamecnik, J

AU - Mühlebner, A

AU - Aronica, E

PY - 2016/4/28

Y1 - 2016/4/28

N2 - 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.

AB - 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.

KW - Cortical tuber

KW - Epigenetic regulation

KW - Inflammation

KW - Interleukin-1β

KW - Tuberous sclerosis complex

U2 - 10.1007/s12031-016-0750-7

DO - 10.1007/s12031-016-0750-7

M3 - Article

C2 - 27122151

SN - 0895-8696

VL - 59

SP - 464

EP - 470

JO - Journal of molecular neuroscience

JF - Journal of molecular neuroscience

IS - 4

ER -

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

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