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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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 - 1 Aug 2016
Externally published	Yes

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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.",

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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

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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 - 2016/8/1

Y1 - 2016/8/1

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.

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SN - 0895-8696

VL - 59

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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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