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Nat Genet. 2019 Oct;51(10):1494-1505. doi: 10.1038/s41588-019-0505-9. Epub 2019 Sep 30.

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

Author information

1
Program in Biomedical Informatics, Stanford University, Stanford, CA, USA.
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
3
Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
4
Department of Genetics, Stanford University, Stanford, CA, USA.
5
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
6
Department of Radiology, Stanford University, Stanford, CA, USA.
7
Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
8
Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
9
Division of Neonatology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
10
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
11
Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, San Francisco, CA, USA. lindsey.criswell@ucsf.edu.
12
Department of Genetics, Stanford University, Stanford, CA, USA. wjg@stanford.edu.
13
Department of Applied Physics, Stanford University, Stanford, CA, USA. wjg@stanford.edu.
14
Chan Zuckerberg Biohub, San Francisco, CA, USA. wjg@stanford.edu.
15
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
16
Diabetes Center, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
17
Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. alexander.marson@ucsf.edu.
18
Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
19
Chan Zuckerberg Biohub, San Francisco, CA, USA. alexander.marson@ucsf.edu.
20
UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
21
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. alexander.marson@ucsf.edu.
22
Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. alexander.marson@ucsf.edu.
23
Department of Genetics, Stanford University, Stanford, CA, USA. pritch@stanford.edu.
24
Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. pritch@stanford.edu.
25
Department of Biology, Stanford University, Stanford, CA, USA. pritch@stanford.edu.

Abstract

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.

PMID:
31570894
PMCID:
PMC6858557
[Available on 2020-03-30]
DOI:
10.1038/s41588-019-0505-9

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