The three-dimensional landscape of chromatin accessibility in Alzheimer’s disease

To characterize the dysregulation of chromatin accessibility in Alzheimer’s disease (AD), we generated 636 ATAC-seq libraries in neurons and non-neurons 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 inter-individual 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 regulatory networks. For one of the most AD-perturbed transcription factors, USF2, we validated its regulatory effect on lysosomal genes. Overall, we applied a systematic approach to understand the role of the 3D genome in AD. We provide all data as an online resource for widespread community-based analysis.

Data: Raw data & UCSC hub

Raw and processed data are available at Synapse. You can also view the open chromatin tracks in the UCSC genome browser as a track hub:

Description of UCSC tracks: