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| Status |
Public on Oct 16, 2020 |
| Title |
ChIP_HD_KI_3 |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Temporal dynamics and mechanisms underlying epigenetic changes in Huntington’s disease (HD),a neurodegenerative disease primarily affecting the striatum, remain unclear. Using slow progressing HDknockinmice,we have generated chromatin immunoprecipitation coupled with sequencing data for RNA polymerase II and histone modifications associated with active enhancers (H3K27ac) and repressive chromatin (H3K27me3), from neuronal, non-neuronal and bulk striatal tissue at two early disease stages. Data integration with cell type-specific transcriptomic databases shows that the HD mutation early accelerates age-related reprogramming of neuronal and glial cell identities at both epigenetic and transcriptional levels. Circular chromosome conformation capture followed by sequencing data using HD mouse striatum showed alterations both at neuronal super-enhancer and CAG expanded disease loci. Using these data to model higher-order chromatin architecture indicated that HD CAG expansion mutation impairs chromatin insulation and gene regulation. Thus, both age-dependent and disease locus-specific mechanisms contribute to early remodelling of chromatin structure in HD striatum.
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| Overall design |
ChIP-sequencing of H3K27ac, H3K27me3 and RNA Pol II for WT and Knock-In Q140 mice striatum at 2 and 6 months of age (2 replicates per condition); H3K9me3 for WT and Knock-In Q140 mice striatum at 6 months of age (1 replicate) and of H3K27ac and H3K27me3 in striatal NeuN sorted nuclei from WT mice at 20 weeks of age (2 replicates)
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| Contributor(s) |
Merienne K, Alcala-Vida R, Seguin J |
| Citation(s) |
33441541 |
| |
| Submission date |
Feb 03, 2020 |
| Last update date |
Jan 20, 2021 |
| Contact name |
Jonathan Seguin |
| E-mail(s) |
seguin.jonathan@gmail.com
|
| Phone |
+333688245252
|
| Organization name |
UKBB-DBM
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| Lab |
group of Prof. Schwaller
|
| Street address |
Spitalstrasse 33
|
| City |
Basel |
| ZIP/Postal code |
CH-4056 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA604595 |
| SRA |
SRP246914 |
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