The three-dimensional landscape of cortical chromatin accessibility in Alzheimer's disease.
The three-dimensional landscape of cortical chromatin accessibility in Alzheimer's disease.
复制标题
阿尔茨海默氏病皮质染色质可及性的三维景观。
DOI：
10.1038/s41593-022-01166-7
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发表时间：
2022-10
影响因子：
25
通讯作者：
Roussos, Panos
中科院分区：
文献类型：
--
作者：
Bendl, Jaroslav;Hauberg, Mads E.;Girdhar, Kiran;Im, Eunju;Vicari, James M.;Rahman, Samir;Fernando, Michael B.;Townsley, Kayla G.;Dong, Pengfei;Misir, Ruth;Kleopoulos, Steven P.;Reach, Sarah M.;Apontes, Pasha;Zeng, Biao;Zhang, Wen;Voloudakis, Georgios;Brennand, Kristen J.;Nixon, Ralph A.;Haroutunian, Vahram;Hoffman, Gabriel E.;Fullard, John F.;Roussos, Panos
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. The authors generated the largest epigenome atlas of post-mortem brains with Alzheimer’s disease. They reported regulatory genomic signatures associated with AD, including variability in open chromatin regions, TF networks and cis-regulatory domains.
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影响因子：
46.9
作者：
Ernst J;Kellis M
通讯作者：
Kellis M
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
15.1
作者：
Barrera J;Song L;Gamache JE;Garrett ME;Safi A;Yun Y;Premasinghe I;Sprague D;Chipman D;Li J;Fradin H;Soldano K;Gordân R;Ashley-Koch AE;Crawford GE;Chiba-Falek O
通讯作者：
Chiba-Falek O
影响因子：
9.8
作者：
De Jager, Philip L.;Ma, Yiyi;Bennett, David A.
通讯作者：
Bennett, David A.
影响因子：
3.5
作者：
Acquaah-Mensah, George K.;Taylor, Ronald C.
通讯作者：
Taylor, Ronald C.