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The three-dimensional landscape of cortical chromatin accessibility in Alzheimer's disease.
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.
Afiliação
  • Bendl J; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Hauberg ME; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Girdhar K; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Im E; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Vicari JM; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rahman S; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Fernando MB; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Townsley KG; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • Dong P; The Lundbeck Foundation Initiative of Integrative Psychiatric Research (iPSYCH), Aarhus University, Aarhus, Denmark.
  • Misir R; Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark.
  • Kleopoulos SP; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Reach SM; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Apontes P; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Zeng B; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Zhang W; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Voloudakis G; Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
  • Brennand KJ; Department of Psychiatry, New York University Langone Health, New York, NY, USA.
  • Nixon RA; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Haroutunian V; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Hoffman GE; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Fullard JF; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Roussos P; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Neurosci ; 25(10): 1366-1378, 2022 10.
Article em En | MEDLINE | ID: mdl-36171428
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article