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Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects

BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the...

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Autores principales: Lintas, Carla, Sacco, Roberto, Persico, Antonio M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850686/
https://www.ncbi.nlm.nih.gov/pubmed/27134686
http://dx.doi.org/10.1186/s11689-016-9151-z
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author Lintas, Carla
Sacco, Roberto
Persico, Antonio M.
author_facet Lintas, Carla
Sacco, Roberto
Persico, Antonio M.
author_sort Lintas, Carla
collection PubMed
description BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5′ region of the RELN gene promoter, spanning from −458 to −223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3′ promoter region, spanning from −222 to +1 bp. The most upstream promoter region (−458 to −364 bp) is methylated only in ASD brains, while the most downstream region (−131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s11689-016-9151-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-48506862016-04-30 Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects Lintas, Carla Sacco, Roberto Persico, Antonio M. J Neurodev Disord Research BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5′ region of the RELN gene promoter, spanning from −458 to −223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3′ promoter region, spanning from −222 to +1 bp. The most upstream promoter region (−458 to −364 bp) is methylated only in ASD brains, while the most downstream region (−131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s11689-016-9151-z) contains supplementary material, which is available to authorized users. BioMed Central 2016-04-29 /pmc/articles/PMC4850686/ /pubmed/27134686 http://dx.doi.org/10.1186/s11689-016-9151-z Text en © Lintas et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lintas, Carla
Sacco, Roberto
Persico, Antonio M.
Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
title Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
title_full Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
title_fullStr Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
title_full_unstemmed Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
title_short Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
title_sort differential methylation at the reln gene promoter in temporal cortex from autistic and typically developing post-puberal subjects
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850686/
https://www.ncbi.nlm.nih.gov/pubmed/27134686
http://dx.doi.org/10.1186/s11689-016-9151-z
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