Genetic determinants of co-accessible chromatin regions in activated T cells across humans

Rachel E. Gate, Christine S. Cheng, Aviva P. Aiden, Atsede Siba, Marcin Tabaka, Dmytro Lituiev, Ido Machol, M. Grace Gordon, Meena Subramaniam, Muhammad Shamim, Kendrick L. Hougen, Ivo Wortman, Su Chen Huang, Neva C. Durand, Ting Feng, Philip L. de Jager, Howard Y. Chang, Erez Lieberman Aiden, Christophe Benoist, Michael BeerChun J. Ye, Aviv Regev

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalNature Genetics
DOIs
StateAccepted/In press - Jul 9 2018

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Chromatin
T-Lymphocytes
Gene Expression
Autoimmune Diseases
RNA
Health
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Gate, R. E., Cheng, C. S., Aiden, A. P., Siba, A., Tabaka, M., Lituiev, D., ... Regev, A. (Accepted/In press). Genetic determinants of co-accessible chromatin regions in activated T cells across humans. Nature Genetics, 1-11. https://doi.org/10.1038/s41588-018-0156-2

Genetic determinants of co-accessible chromatin regions in activated T cells across humans. / Gate, Rachel E.; Cheng, Christine S.; Aiden, Aviva P.; Siba, Atsede; Tabaka, Marcin; Lituiev, Dmytro; Machol, Ido; Gordon, M. Grace; Subramaniam, Meena; Shamim, Muhammad; Hougen, Kendrick L.; Wortman, Ivo; Huang, Su Chen; Durand, Neva C.; Feng, Ting; de Jager, Philip L.; Chang, Howard Y.; Aiden, Erez Lieberman; Benoist, Christophe; Beer, Michael; Ye, Chun J.; Regev, Aviv.

In: Nature Genetics, 09.07.2018, p. 1-11.

Research output: Contribution to journalArticle

Gate, RE, Cheng, CS, Aiden, AP, Siba, A, Tabaka, M, Lituiev, D, Machol, I, Gordon, MG, Subramaniam, M, Shamim, M, Hougen, KL, Wortman, I, Huang, SC, Durand, NC, Feng, T, de Jager, PL, Chang, HY, Aiden, EL, Benoist, C, Beer, M, Ye, CJ & Regev, A 2018, 'Genetic determinants of co-accessible chromatin regions in activated T cells across humans', Nature Genetics, pp. 1-11. https://doi.org/10.1038/s41588-018-0156-2
Gate, Rachel E. ; Cheng, Christine S. ; Aiden, Aviva P. ; Siba, Atsede ; Tabaka, Marcin ; Lituiev, Dmytro ; Machol, Ido ; Gordon, M. Grace ; Subramaniam, Meena ; Shamim, Muhammad ; Hougen, Kendrick L. ; Wortman, Ivo ; Huang, Su Chen ; Durand, Neva C. ; Feng, Ting ; de Jager, Philip L. ; Chang, Howard Y. ; Aiden, Erez Lieberman ; Benoist, Christophe ; Beer, Michael ; Ye, Chun J. ; Regev, Aviv. / Genetic determinants of co-accessible chromatin regions in activated T cells across humans. In: Nature Genetics. 2018 ; pp. 1-11.
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