DNA methylation in demyelinated multiple sclerosis hippocampus

Abstract Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the human central nervous system (CNS). Memory impairments and hippocampal demyelination are common features in MS patients. Our previous data have shown that demyelination alters neuronal gene expression in the hippocam...

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Autores principales:	Anthony M. Chomyk, Christina Volsko, Ajai Tripathi, Sadie A. Deckard, Bruce D. Trapp, Robert J. Fox, Ranjan Dutta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f24d60627be461e9f277645c33faa5b
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spelling	oai:doaj.org-article:0f24d60627be461e9f277645c33faa5b2021-12-02T16:06:23ZDNA methylation in demyelinated multiple sclerosis hippocampus10.1038/s41598-017-08623-52045-2322https://doaj.org/article/0f24d60627be461e9f277645c33faa5b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08623-5https://doaj.org/toc/2045-2322Abstract Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the human central nervous system (CNS). Memory impairments and hippocampal demyelination are common features in MS patients. Our previous data have shown that demyelination alters neuronal gene expression in the hippocampus. DNA methylation is a common epigenetic modifier of gene expression. In this study, we investigated whether DNA methylation is altered in MS hippocampus following demyelination. Our results show that mRNA levels of DNA methyltransferase were increased in demyelinated MS hippocampus, while de-methylation enzymes were decreased. Comparative methylation profiling identify hypo-methylation within upstream sequences of 6 genes and hyper-methylation of 10 genes in demyelinated MS hippocampus. Genes identified in the current study were also validated in an independent microarray dataset generated from MS hippocampus. Independent validation using RT-PCR revealed that DNA methylation inversely correlated with mRNA levels of the candidate genes. Queries across cell-specific databases revealed that a majority of the candidate genes are expressed by astrocytes and neurons in mouse and human CNS. Taken together, our results expands the list of genes previously identified in MS hippocampus and establish DNA methylation as a mechanism of altered gene expression in MS hippocampus.Anthony M. ChomykChristina VolskoAjai TripathiSadie A. DeckardBruce D. TrappRobert J. FoxRanjan DuttaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anthony M. Chomyk Christina Volsko Ajai Tripathi Sadie A. Deckard Bruce D. Trapp Robert J. Fox Ranjan Dutta DNA methylation in demyelinated multiple sclerosis hippocampus
description	Abstract Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the human central nervous system (CNS). Memory impairments and hippocampal demyelination are common features in MS patients. Our previous data have shown that demyelination alters neuronal gene expression in the hippocampus. DNA methylation is a common epigenetic modifier of gene expression. In this study, we investigated whether DNA methylation is altered in MS hippocampus following demyelination. Our results show that mRNA levels of DNA methyltransferase were increased in demyelinated MS hippocampus, while de-methylation enzymes were decreased. Comparative methylation profiling identify hypo-methylation within upstream sequences of 6 genes and hyper-methylation of 10 genes in demyelinated MS hippocampus. Genes identified in the current study were also validated in an independent microarray dataset generated from MS hippocampus. Independent validation using RT-PCR revealed that DNA methylation inversely correlated with mRNA levels of the candidate genes. Queries across cell-specific databases revealed that a majority of the candidate genes are expressed by astrocytes and neurons in mouse and human CNS. Taken together, our results expands the list of genes previously identified in MS hippocampus and establish DNA methylation as a mechanism of altered gene expression in MS hippocampus.
format	article
author	Anthony M. Chomyk Christina Volsko Ajai Tripathi Sadie A. Deckard Bruce D. Trapp Robert J. Fox Ranjan Dutta
author_facet	Anthony M. Chomyk Christina Volsko Ajai Tripathi Sadie A. Deckard Bruce D. Trapp Robert J. Fox Ranjan Dutta
author_sort	Anthony M. Chomyk
title	DNA methylation in demyelinated multiple sclerosis hippocampus
title_short	DNA methylation in demyelinated multiple sclerosis hippocampus
title_full	DNA methylation in demyelinated multiple sclerosis hippocampus
title_fullStr	DNA methylation in demyelinated multiple sclerosis hippocampus
title_full_unstemmed	DNA methylation in demyelinated multiple sclerosis hippocampus
title_sort	dna methylation in demyelinated multiple sclerosis hippocampus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0f24d60627be461e9f277645c33faa5b
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_version_	1718385006337851392

DNA methylation in demyelinated multiple sclerosis hippocampus

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