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Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains.

ABSTRACT: Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis-affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts. Genes regulating oligodendrocyte survival, such as BCL2L2 and NDRG1, were hypermethylated and expressed at lower levels in multiple sclerosis-affected brains than in controls, while genes related to proteolytic processing (for example, LGMN, CTSZ) were hypomethylated and expressed at higher levels. These results were not due to differences in cellular composition between multiple sclerosis and controls. Thus, epigenomic changes in genes affecting oligodendrocyte susceptibility to damage are detected in pathology-free areas of multiple sclerosis-affected brains.

SUBMITTER: Huynh JL

PROVIDER: S-EPMC3934491 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains.

Huynh Jimmy L JL Garg Paras P Thin Tin Htwe TH Yoo Seungyeul S Dutta Ranjan R Trapp Bruce D BD Haroutunian Vahram V Zhu Jun J Donovan Michael J MJ Sharp Andrew J AJ Casaccia Patrizia P

Nature neuroscience 20131124 1

Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis-affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independen ...[more]

PMID: 24270187

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Dataset Information

Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains.

Publications

Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains.

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