Analysis of chromatin organization and gene expression in T cells identifies functional genes for rheumatoid arthritis

Jing Yang, Amanda McGovern, Paul Martin, Kate Duffus, Xiangyu Ge, Peyman Zarrineh, Andrew P. Morris, Antony Adamson, Peter Fraser, Magnus Rattray () and Stephen Eyre ()
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Jing Yang: University of Manchester
Amanda McGovern: University of Manchester
Paul Martin: University of Manchester
Kate Duffus: University of Manchester
Xiangyu Ge: University of Manchester
Peyman Zarrineh: University of Manchester
Andrew P. Morris: University of Manchester
Antony Adamson: University of Manchester
Peter Fraser: Florida State University
Magnus Rattray: University of Manchester
Stephen Eyre: University of Manchester

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Genome-wide association studies have identified genetic variation contributing to complex disease risk. However, assigning causal genes and mechanisms has been more challenging because disease-associated variants are often found in distal regulatory regions with cell-type specific behaviours. Here, we collect ATAC-seq, Hi-C, Capture Hi-C and nuclear RNA-seq data in stimulated CD4+ T cells over 24 h, to identify functional enhancers regulating gene expression. We characterise changes in DNA interaction and activity dynamics that correlate with changes in gene expression, and find that the strongest correlations are observed within 200 kb of promoters. Using rheumatoid arthritis as an example of T cell mediated disease, we demonstrate interactions of expression quantitative trait loci with target genes, and confirm assigned genes or show complex interactions for 20% of disease associated loci, including FOXO1, which we confirm using CRISPR/Cas9.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18180-7

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DOI: 10.1038/s41467-020-18180-7

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