TY - JOUR T1 - The three-dimensional landscape of chromatin accessibility in Alzheimer’s disease JF - bioRxiv DO - 10.1101/2021.01.11.426303 SP - 2021.01.11.426303 AU - Jaroslav Bendl AU - Mads E. Hauberg AU - Kiran Girdhar AU - Eunju Im AU - James M. Vicari AU - Samir Rahman AU - Pengfei Dong AU - Ruth Misir AU - Steven P. Kleopoulos AU - Sarah M. Reach AU - Pasha Apontes AU - Biao Zeng AU - Wen Zhang AU - Georgios Voloudakis AU - Ralph A. Nixon AU - Vahram Haroutunian AU - Gabriel E. Hoffman AU - John F. Fullard AU - Panos Roussos Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/12/2021.01.11.426303.abstract N2 - Much is still unknown about the neurobiology of Alzheimer’s disease (AD). To better understand AD, we generated 636 ATAC-seq libraries from cases and controls to construct detailed genomewide chromatin accessibility maps of neurons and non-neurons from two AD-affected brain regions, the entorhinal cortex and superior temporal gyrus. By analyzing a total of 19.6 billion read pairs, we expanded the known repertoire of regulatory sequences in the human brain. Multi-omic data integration associated global patterns of chromatin accessibility with gene expression and identified cell-specific enhancer-promoter interactions. Using inter-individual variation in chromatin accessibility, we define cis-regulatory domains capturing the 3D structure of the genome. Multifaceted analyses uncovered disease associated perturbations impacting chromatin accessibility, transcription factor regulatory networks and the 3D genome, and implicated transcriptional dysregulation in AD. Overall, we applied a systematic approach to understand the role of the 3D genome in AD and to illuminate novel disease biology that can advance diagnosis and therapy.Competing Interest StatementThe authors have declared no competing interest. ER -