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

Author(s): 
Huynh, Jimmy L.
Garg, Paras
Thin, Tin Htwe
Yoo, Seungyeul
Dutta, Ranjan
Trapp, Bruce D.
Haroutunian, Vahram
Zhu, Jun
Donovan, Michael J.
Sharp, Andrew J.
Casaccia, Patrizia
Item Type: 
Journal Article
Publication Title: 
Nature Neuroscience
Journal Abbreviation: 
Nat. Neurosci.
Publication Date: 
2014-01
Publication Year: 
2014
Pages: 
121-130
Volume: 
17
Issue: 
1
ISSN: 
1546-1726
DOI: 
10.1038/nn.3588
Library Catalog: 
PubMed
Extra: 
PMID: 24270187 PMCID: PMC3934491

Turabian/Chicago Citation

Jimmy L. Huynh, Paras Garg, Tin Htwe Thin, Seungyeul Yoo, Ranjan Dutta, Bruce D. Trapp, Vahram Haroutunian, Jun Zhu, Michael J. Donovan, Andrew J. Sharp and Patrizia Casaccia. 2014-01. "Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains." Nature Neuroscience 17: 1: 121-130. 10.1038/nn.3588.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1038/nn.3588 | issn = 1546-1726 | volume = 17 | pages = 121-130 | last = Huynh | first = Jimmy L. | coauthors = Garg, Paras, Thin, Tin Htwe, Yoo, Seungyeul, Dutta, Ranjan, Trapp, Bruce D., Haroutunian, Vahram, Zhu, Jun, Donovan, Michael J., Sharp, Andrew J., Casaccia, Patrizia | title = Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains | journal = Nature Neuroscience | date = 2014-01 | pmid = | pmc = }} </ref>