作者
Jaroslav Bendl, Mads E Hauberg, Kiran Girdhar, Eunju Im, James M Vicari, Samir Rahman, Michael B Fernando, Kayla G Townsley, Pengfei Dong, Ruth Misir, Steven P Kleopoulos, Sarah M Reach, Pasha Apontes, Biao Zeng, Wen Zhang, Georgios Voloudakis, Kristen J Brennand, Ralph A Nixon, Vahram Haroutunian, Gabriel E Hoffman, John F Fullard, Panos Roussos
发表日期
2022/10
期刊
Nature neuroscience
卷号
25
期号
10
页码范围
1366-1378
出版商
Nature Publishing Group US
简介
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 …
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J Bendl, ME Hauberg, K Girdhar, E Im, JM Vicari… - Nature neuroscience, 2022