| Literature DB >> 36171428 |
Jaroslav Bendl1,2,3,4,5, Mads E Hauberg2,4,6,7,8, Kiran Girdhar1,2,3,4,5, Eunju Im9,10, James M Vicari1,2,3,4,5,11, Samir Rahman1,2,3,4,5, Michael B Fernando2,11,12,13, Kayla G Townsley2,11,12, Pengfei Dong1,2,3,4,5, Ruth Misir2,4,5, Steven P Kleopoulos1,2,3,4,5, Sarah M Reach2,4,5, Pasha Apontes2,4,5, Biao Zeng1,2,3,4,5, Wen Zhang1,2,3,4,5, Georgios Voloudakis1,2,4, Kristen J Brennand2,4,12,13,14, Ralph A Nixon9,10,15,16, Vahram Haroutunian2,4,12,17, Gabriel E Hoffman1,3,5, John F Fullard1,2,3,4,5, Panos Roussos18,19,20,21,22,23,24.
Abstract
To characterize the dysregulation of chromatin accessibility in Alzheimer's disease (AD), we generated 636 ATAC-seq libraries from neuronal and nonneuronal nuclei isolated from the superior temporal gyrus and entorhinal cortex of 153 AD cases and 56 controls. By analyzing a total of ~20 billion read pairs, we expanded the repertoire of known open chromatin regions (OCRs) in the human brain and identified cell-type-specific enhancer-promoter interactions. We show that interindividual variability in OCRs can be leveraged to identify cis-regulatory domains (CRDs) that capture the three-dimensional structure of the genome (3D genome). We identified AD-associated effects on chromatin accessibility, the 3D genome and transcription factor (TF) regulatory networks. For one of the most AD-perturbed TFs, USF2, we validated its regulatory effect on lysosomal genes. Overall, we applied a systematic approach to understanding the role of the 3D genome in AD. We provide all data as an online resource for widespread community-based analysis.Entities:
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Year: 2022 PMID： 36171428 PMCID： PMC9581463 DOI： 10.1038/s41593-022-01166-7
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 28.771