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Title: DNA methylation profiling in human Huntington's Disease brain      
dateReleased:
03-11-2016
description:
Despite extensive progress in Huntington’s Disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are highest in brain and testes, is currently unknown. To investigate the role of DNA methylation in HD pathogenesis and tissue-specific expression of HTT, we utilized the Illumina HumanMethylation450K BeadChip array to measure DNA methylation in a cohort of age-matched HD and control human cortex and liver tissues. In cortex samples, we found minimal evidence of HD-associated DNA methylation at probed sites after correction for cell heterogeneity but did observe an association to age of disease onset. By contrast, comparison of matched cortex and liver samples revealed tissue-specific DNA methylation of the HTT gene region at 38 sites (FDR < 0.05). Importantly, we identified a novel differentially methylated binding site in the HTT proximal promoter for the transcription factor CTCF. This CTCF site displayed increased occupancy in cortex, where HTT expression is higher, compared to liver. Additionally, CTCF silencing reduced the activity of a HTT promoter-reporter construct, suggesting that CTCF plays a role in regulating HTT promoter function. Overall, although we were unable to detect HD-associated DNA methylation alterations at queried sites, we found that DNA methylation may be correlated to age of disease onset in cortex tissues. Moreover, our data suggest that DNA methylation may, in part, contribute to tissue-specific HTT transcription through differential CTCF occupancy. The Illumina Infinium HumanMethylation450 Beadchip was used to obtain genome-wide DNA methylation measures in human cortex tissue (n = 13), with a subset of matched liver tissues (n = 5) , from a cohort of HD (n = 7) and control (n = 6) individuals in order to identify potential HD-related DNA methylation aberration in the brain as well as tissue-specific DNA methylation variation at the HTT gene locus.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-79064
refinement:
raw
alternateIdentifiers:
79064
keywords:
functional genomics
dateModified:
03-20-2016
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-13534
name:
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482_v.1.1)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-79064/E-GEOD-79064.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-79064/E-GEOD-79064.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE79064
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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