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Series GSE44854 Query DataSets for GSE44854
Status Public on Jun 20, 2013
Title Histone deacetylation-dependent and -independent transcriptional dysregulation in early-onset polyglutamine disease
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Transcriptional dysregulation is an important early feature of polyglutamine diseases. One of its proposed causes is defective neuronal histone acetylation, but important aspects of this hypothesis, such as the precise genomic topography of acetylation deficits and the relationship between transcriptional and acetylation alterations at the whole-genome level, remain unknown. The new techniques for the mapping of histone posttranslational modifications at genomic scale enable such global analyses and are challenging important assumptions concerning the role of specific histone modifications in gene expression. We examined here the genome-wide correlation of histone acetylation and gene expression defects in a mouse model of early-onset Huntington’s disease. Our analyses identified hundreds of loci that were hypoacetylated for H3K9,14 and H4K12 in the chromatin of these mice. Surprisingly, few genes with altered transcript levels in mutant mice showed significant changes in these acetylation marks and vice versa. Our screen, however, identified a subset of genes in which H3K9,14 deacetylation and transcriptional dysregulation concur. Genes in this group were consistently affected in different brain areas, mouse models and tissue from patients, which suggests a role in the etiology of this pathology. Overall, the combination of histone acetylation and gene expression screenings demonstrates that histone deacetylation and transcriptional dysregulation are two early, largely independent, manifestations of polyglutamine disease and suggests that additional epigenetic marks or mechanisms are required for explaining the full range of transcriptional alterations associated with this disorder.
Overall design Examination of 2 different histone modifications in the hippocampus of wild-type and HD mice (PrP-htt-N171-82Q (Schilling et al., 1999)). Samples were obtained from 10 week old mice.
Citation(s) 23785159
Submission date Mar 05, 2013
Last update date Sep 16, 2019
Contact name Angel Barco
Organization name Instituto de Neurociencias (UMH-CSIC)
Street address Av. Santiago Ramón y Cajal
City Sant Joan d'Alacant
State/province Alicante
ZIP/Postal code 03550
Country Spain
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (6)
GSM1092643 GBD28_AcH3K9,14_ChIPseq
GSM1092644 GBD29_AcH3K9,14_ChIPseq
GSM1092645 GBD30_AcH4K12_ChIPseq
This SubSeries is part of SuperSeries:
GSE44855 Genomic landscape of transcriptional and epigenetic dysregulation in a mouse model of early onset Huntington's disease
BioProject PRJNA192577
SRA SRP019239

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Supplementary file Size Download File type/resource
GSE44854_RAW.tar 61.2 Mb (http)(custom) TAR (of WIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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