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| Status |
Public on Nov 10, 2020 |
| Title |
Huntington’s disease as a lamin B1 nuclear envelopathy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Lamins, the major structural proteins within the nuclear lamina, are crucial for the functionality of cellular nucleus and their alterations are involved in the so-called laminopathies. We previously found that Huntington’s disease (HD), a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the huntingtin (htt) gene, courses with increased lamin B protein levels in specific brain regions in both mouse models and patients. We now show that these changes are mostly restricted to lamin B1, occur in striatal medium-sized spiny neurons and CA1 hippocampal neurons, and are accompanied by altered nuclear morphology, nucleocytoplasmic transport disruption and un-structuring of lamin-associated chromatin domains. Normalization of lamin B1 levels by betulinic acid administration in the R6/1 mouse model of HD results in beneficial restoring of nuclear lamina homeostasis and prevention of motor and cognitive dysfunction, opening a window for a new therapeutic approach for HD and other B1-type laminophaties.
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| Overall design |
ChIP-seq (36 samples), RNA-seq (18 samples) and ATAC-seq (6 samples) of 30-week-old WT and R6/1 mice hippocampus. WT means Wild-type mice and R6/1 means R6/1 Huntington's disease transgenic mice (PubMed ID 8898202)
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| |
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| Contributor(s) |
Alcalá-Vida R, Garcia-Forn M, Pérez-Navarro E, Blanco E |
| Citation(s) |
33369245 |
| |
| Submission date |
Nov 04, 2019 |
| Last update date |
Feb 09, 2021 |
| Contact name |
Enrique Blanco |
| E-mail(s) |
enrique.blanco@crg.eu
|
| Phone |
+34 93 316 01 00
|
| Organization name |
Center for Genomic Regulation (CRG)
|
| Department |
Gene Regulation, Stem Cells and Cancer
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| Lab |
Epigenetic Events in Cancer (L. Di Croce's lab)
|
| Street address |
Dr. Aiguader 88
|
| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (60)
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| Relations |
| BioProject |
PRJNA587460 |
| SRA |
SRP228541 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE139884_ATAC_R61_R1.bedgraph.gz |
92.8 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_ATAC_R61_R2.bedgraph.gz |
104.8 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_ATAC_R61_R3.bedgraph.gz |
106.9 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_ATAC_WT_R1.bedgraph.gz |
97.9 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_ATAC_WT_R2.bedgraph.gz |
96.5 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_ATAC_WT_R3.bedgraph.gz |
100.4 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_ChIP_LB1-INPUT_R61.bedgraph.gz |
137.2 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_ChIP_LB1-INPUT_WT.bedgraph.gz |
137.2 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE139884_EDD_LB1-INPUT_R61_peaks.bed.gz |
2.6 Kb |
(ftp)(http) |
BED |
| GSE139884_EDD_LB1-INPUT_WT_peaks.bed.gz |
2.3 Kb |
(ftp)(http) |
BED |
| GSE139884_RNA_DESeq2_RPKMs.txt.gz |
2.7 Mb |
(ftp)(http) |
TXT |
| GSE139884_RNA_DESeq2_results.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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