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Series GSE43431 Query DataSets for GSE43431
Status Public on Jan 24, 2013
Title Extensive changes in DNA methylation are associated with expression of mutant huntingtin [mRNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The earliest stages of Huntington’s disease are marked by changes in gene expression that are caused in an indirect and poorly understood manner by polyglutamine expansions in the huntingtin protein (HTT). To explore the hypothesis DNA methylation may be altered in cells expressing mutated HTT, we use reduced-representation bisulfite sequencing (RRBS) to map sites of DNA methylation in cells carrying either wild-type or mutant HTT. We find that a large fraction of the genes that change in expression in the presence of mutant huntingtin demonstrate significant changes in DNA methylation. Regions with low CpG content, which have previously been shown to undergo methylation changes in response to neuronal activity, are disproportionately affected. Based on the sequence of regions that change in methylation, we identify AP-1 and SOX2 as transcriptional regulators associated with DNA methylation changes, and we confirm these hypotheses using genome-wide chromatin immunoprecipitation (ChIP-Seq). Our findings suggest new mechanisms for the effects of polyglutamine-expanded HTT. These results also raise important questions about the potential effects of changes in DNA methylation on neurogenesis and at later stages, cognitive decline in Huntington’s patients.
 
Overall design mRNA-seq in STHdhQ7/Q7 and STHdhQ111/Q111 cells
 
Contributor(s) Ng CW, Fraenkel E
Citation(s) 23341638
Submission date Jan 10, 2013
Last update date May 15, 2019
Contact name Christopher Ng
Organization name Massachusetts Institute of Technology
Street address 77 Massachusetts Ave.
City Cambridge
State/province Massachusetts
ZIP/Postal code 02139
Country USA
 
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (2)
GSM1062371 RNA_STHdhQ7_reps1-3
GSM1062372 RNA_STHdhQ111_reps1-3
This SubSeries is part of SuperSeries:
GSE43433 Extensive changes in DNA methylation are associated with expression of mutant huntingtin
Relations
BioProject PRJNA186417
SRA SRP017913

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43431_mRNA_STHdh_CUFF_gene_exp.diff.txt.gz 849.3 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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