|
| Status |
Public on Jan 24, 2013 |
| Title |
Extensive changes in DNA methylation are associated with expression of mutant huntingtin [MeDIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation 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.
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| |
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| Overall design |
MeDIP-seq in STHdhQ7/Q7 and STHdhQ111/Q111 cells
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| |
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| 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 |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE43433 |
Extensive changes in DNA methylation are associated with expression of mutant huntingtin |
|
| Relations |
| BioProject |
PRJNA186416 |
| SRA |
SRP017912 |
