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Landscape of stimulation-responsive chromatin across diverse human immune cells.

Publication ,  Journal Article
Calderon, D; Nguyen, MLT; Mezger, A; Kathiria, A; Müller, F; Nguyen, V; Lescano, N; Wu, B; Trombetta, J; Ribado, JV; Knowles, DA; Gao, Z ...
Published in: Nat Genet
October 2019

A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2019

Volume

51

Issue

10

Start / End Page

1494 / 1505

Location

United States

Related Subject Headings

  • Transcriptome
  • T-Lymphocytes
  • Response Elements
  • Polysaccharides
  • Killer Cells, Natural
  • Interleukin-4
  • Interleukin-2
  • Humans
  • Gene Expression Regulation
  • Epigenesis, Genetic
 

Citation

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Calderon, D., Nguyen, M. L. T., Mezger, A., Kathiria, A., Müller, F., Nguyen, V., … Pritchard, J. K. (2019). Landscape of stimulation-responsive chromatin across diverse human immune cells. Nat Genet, 51(10), 1494–1505. https://doi.org/10.1038/s41588-019-0505-9
Calderon, Diego, Michelle L. T. Nguyen, Anja Mezger, Arwa Kathiria, Fabian Müller, Vinh Nguyen, Ninnia Lescano, et al. “Landscape of stimulation-responsive chromatin across diverse human immune cells.Nat Genet 51, no. 10 (October 2019): 1494–1505. https://doi.org/10.1038/s41588-019-0505-9.
Calderon D, Nguyen MLT, Mezger A, Kathiria A, Müller F, Nguyen V, et al. Landscape of stimulation-responsive chromatin across diverse human immune cells. Nat Genet. 2019 Oct;51(10):1494–505.
Calderon, Diego, et al. “Landscape of stimulation-responsive chromatin across diverse human immune cells.Nat Genet, vol. 51, no. 10, Oct. 2019, pp. 1494–505. Pubmed, doi:10.1038/s41588-019-0505-9.
Calderon D, Nguyen MLT, Mezger A, Kathiria A, Müller F, Nguyen V, Lescano N, Wu B, Trombetta J, Ribado JV, Knowles DA, Gao Z, Blaeschke F, Parent AV, Burt TD, Anderson MS, Criswell LA, Greenleaf WJ, Marson A, Pritchard JK. Landscape of stimulation-responsive chromatin across diverse human immune cells. Nat Genet. 2019 Oct;51(10):1494–1505.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2019

Volume

51

Issue

10

Start / End Page

1494 / 1505

Location

United States

Related Subject Headings

  • Transcriptome
  • T-Lymphocytes
  • Response Elements
  • Polysaccharides
  • Killer Cells, Natural
  • Interleukin-4
  • Interleukin-2
  • Humans
  • Gene Expression Regulation
  • Epigenesis, Genetic