Analysis of chromatin organization and gene expression in T cells identifies functional genes for rheumatoid arthritis
Authors
Yang, JingMcGovern, Amanda; orcid: 0000-0001-7727-3283
Martin, Paul; orcid: 0000-0002-1016-6851
Duffus, Kate
Ge, Xiangyu
Zarrineh, Peyman
Morris, Andrew P.
Adamson, Antony; orcid: 0000-0002-5408-0013
Fraser, Peter; orcid: 0000-0002-0041-1227
Rattray, Magnus; orcid: 0000-0001-8196-5565; email: magnus.rattray@manchester.ac.uk
Eyre, Stephen; orcid: 0000-0002-1251-6974; email: steve.eyre@manchester.ac.uk
Publication Date
2020-09-02Submitted date
2019-10-22
Metadata
Show full item recordAbstract
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.Citation
Nature Communications, volume 11, issue 1, page 4402Publisher
Nature Publishing Group UKType
articleDescription
From Springer Nature via Jisc Publications RouterHistory: received 2019-10-22, accepted 2020-08-06, registration 2020-08-11, pub-electronic 2020-09-02, online 2020-09-02, collection 2020-12
Publication status: Published
Funder: RCUK | MRC | Medical Research Foundation; doi: https://doi.org/10.13039/501100009187; Grant(s): MR/N00017X/1
Funder: Arthritis Research UK; doi: https://doi.org/10.13039/501100000341; Grant(s): 21754