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| Status |
Public on Mar 07, 2018 |
| Title |
Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Aging is the strongest risk factor for Alzheimer's disease (AD), although the underlying mechanisms remain unclear. The chromatin state, in particular through the mark H4K16ac, has been implicated in aging and thus may play a pivotal role in age-associated neurodegeneration. Here we compared the genome-wide enrichment of H4K16ac in the lateral temporal lobe of AD individuals against both younger and elderly cognitively normal controls. We find that while normal aging leads to H4K16ac enrichment, AD entails dramatic losses of H4K16ac in the proximity of genes linked to aging and AD. Our analysis highlights the presence of three classes of AD-related changes having distinctive functional roles. Furthermore, we discover an association between the genomic locations of significant H4K16ac changes with genetic variants (SNPs) identified in prior AD genome-wide association studies (GWAS) and with expression quantitative trait loci (eQTLs). Our results establish the basis for an epigenetic link between aging and AD.
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| Overall design |
ChIP-seq of H4K16ac in healthy and diseased human brains; using 9 young healthy brains (Young), 10 aged healthy brains (Old), and 12 aged diseased brains (AD); H4K16ac and input are included for each sample
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| Contributor(s) |
Nativio R, Donahue G, Berson A, Gosai SJ, Toledo JB, Amlie-Wolf A, Tuzer F, Torres C, Trojanowski JQ, Wang L, Gregory BD, Johnson FB, Bonini NM, Berger SL |
| Citation(s) |
29507413 |
| Submission date |
Jul 20, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Gregory Donahue |
| Organization name |
The University of Pennsylvania
|
| Department |
Cell & Developmental Biology
|
| Lab |
Zaret Lab
|
| Street address |
3400 Civic Center Blvd, Bldg 421
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (62)
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| This SubSeries is part of SuperSeries: |
| GSE104705 |
Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease |
|
| Relations |
| BioProject |
PRJNA330668 |
| SRA |
SRP078988 |
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