Landscape of stimulation-responsive chromatin across diverse human immune cells

被引：157

作者：

Calderon, Diego ^{[1
]}

Nguyen, Michelle L. T. ^{[2
,3
]}

Mezger, Anja ^{[4
,5
]}

Kathiria, Arwa ^{[4
]}

Mueller, Fabian ^{[4
]}

Nguyen, Vinh ^{[3
]}

Lescano, Ninnia ^{[3
]}

Wu, Beijing ^{[4
]}

Trombetta, John ^{[4
]}

Ribado, Jessica, V ^{[4
]}

Knowles, David A. ^{[4
,6
]}

Gao, Ziyue ^{[4
,7
]}

Blaeschke, Franziska ^{[2
,3
,8
]}

Parent, Audrey, V ^{[3
]}

Burt, Trevor D. ^{[9
,10
]}

Anderson, Mark S. ^{[3
]}

Criswell, Lindsey A. ^{[11
]}

Greenleaf, William J. ^{[4
,12
,13
]}

Marson, Alexander ^{[2
,3
,8
,11
,13
,14
,15
,16
]}

Pritchard, Jonathan K. ^{[4
,7
,17
]}

机构：

[1] Stanford Univ, Program Biomed Informat, Stanford, CA 94305 USA

[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

[4] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[5] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden

[6] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA

[7] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

[8] Univ Calif Berkeley, Innovat Genom Inst, Berkeley, CA 94720 USA

[9] Univ Calif San Francisco, Dept Pediat, Div Neonatol, San Francisco, CA USA

[10] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

[11] Univ Calif San Francisco, Rosalind Russell Ephraim P Engleman Rheumatol Res, San Francisco, CA 94143 USA

[12] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA

[13] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

[14] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[15] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[16] Parker Inst Canc Immunotherapy, San Francisco, CA 94129 USA

[17] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

来源：

NATURE GENETICS | 2019年 / 51卷 / 10期

基金：

瑞典研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; DNA-BINDING; LOCI; ACTIVATION; IDENTIFICATION; ARCHITECTURE; SENSITIVITY; ANNOTATION; ENHANCERS; DISCOVERY;

D O I：

10.1038/s41588-019-0505-9

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1494 / +

页数：14

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