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GEO help: Mouse over screen elements for information. |
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Status |
Public on Oct 16, 2020 |
Title |
4C-seq HD project |
Organism |
Mus musculus |
Experiment type |
Other
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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 |
4C-seq experiment in WT (2 replicates, 9 baits) and Knock-in Q140 homozygous (2 replicates, 9 baits) mice striatum at 6 months of age; WT (1 replicate, 3 baits) and R6/1 (1 replicate, 3 baits) mice striatum at 14 weeks of age and mouse ESC (1 replicate, 1 bait).
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Contributor(s) |
Merienne K, Alcala-Vida R, Seguin J |
Citation(s) |
33441541 |
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Submission date |
Feb 03, 2020 |
Last update date |
Jan 20, 2021 |
Contact name |
Jonathan Seguin |
E-mail(s) |
seguin.jonathan@gmail.com
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Phone |
+333688245252
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Organization name |
UKBB-DBM
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Lab |
group of Prof. Schwaller
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Street address |
Spitalstrasse 33
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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 (43)
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Relations |
BioProject |
PRJNA604602 |
SRA |
SRP246936 |
Supplementary file |
Size |
Download |
File type/resource |
GSE144699_RAW.tar |
68.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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