Genetic determinants of co-accessible chromatin regions in activated T cells across humans
Name
nihms970112.pdf
Description
Accepted version
Size
1.4 MB
Format
Adobe PDF
Checksum (MD5)
0e7f1ff8b19b95e31c678b9631d87477
Author(s)
Regev, Aviv
Date Issued
August 2018
Journal
Nature genetics
Publisher
Springer Nature
Citation
Gate, Rachel E. et al. “Genetic determinants of co-accessible chromatin regions in activated T cells across humans.” Nature genetics 50 (2018): 1140-1150 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4 + T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/S41588-018-0156-2
