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

  • Author(s): Calderon, Diego
  • Nguyen, Michelle LT
  • Mezger, Anja
  • Kathiria, Arwa
  • Müller, Fabian
  • Nguyen, Vinh
  • Lescano, Ninnia
  • Wu, Beijing
  • Trombetta, John
  • Ribado, Jessica V
  • Knowles, David A
  • Gao, Ziyue
  • Blaeschke, Franziska
  • Parent, Audrey V
  • Burt, Trevor D
  • Anderson, Mark S
  • Criswell, Lindsey A
  • Greenleaf, William J
  • Marson, Alexander
  • Pritchard, Jonathan K
  • et al.
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.

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