Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Landscape of stimulation-responsive chromatin across diverse human immune cells

View ORCID ProfileDiego Calderon, Michelle L.T. Nguyen, Anja Mezger, Arwa Kathiria, Vinh Nguyen, Ninnia Lescano, Beijing Wu, John Trombetta, Jessica V. Ribado, David A. Knowles, Ziyue Gao, Audrey V. Parent, Trevor D. Burt, Mark S. Anderson, Lindsey A. Criswell, William J. Greenleaf, Alexander Marson, Jonathan K. Pritchard
doi: https://doi.org/10.1101/409722
Diego Calderon
Stanford University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Diego Calderon
Michelle L.T. Nguyen
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anja Mezger
Stanford University; Karolinska Institutet;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arwa Kathiria
Stanford University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vinh Nguyen
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ninnia Lescano
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Beijing Wu
Stanford University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Trombetta
Stanford University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jessica V. Ribado
Stanford University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Knowles
Stanford University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ziyue Gao
Stanford University; HHMI;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Audrey V. Parent
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Trevor D. Burt
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark S. Anderson
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lindsey A. Criswell
UCSF;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William J. Greenleaf
Stanford University; Chan Zuckerberg Biohub;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Marson
UCSF; Chan Zuckerberg Biohub; UCB
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan K. Pritchard
Stanford University; HHMI;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: pritch@stanford.edu
  • Abstract
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The immune system is controlled by a balanced interplay among specialized cell types transitioning between resting and stimulated states. Despite its importance, the regulatory landscape of this system has not yet been fully characterized. To address this gap, we collected ATAC-seq and RNA-seq data under resting and stimulated conditions for 25 immune cell types from peripheral blood of four healthy individuals, and seven cell types from three fetal thymus samples. We found that stimulation caused widespread chromatin remodeling, including a large class of 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 critical importance of these cell states in autoimmunity. Use of allele-specific read-mapping identified thousands of variants that alter chromatin accessibility in particular conditions. Notably, variants associated with changes in stimulation-specific chromatin accessibility were not enriched for associations with gene expression regulation in whole blood -- a tissue commonly used in eQTL studies. Thus, large-scale maps of variants associated with gene regulation lack a condition important for understanding autoimmunity. As a proof-of-principle we identified variant rs6927172, which links stimulated T cell-specific chromatin dysregulation in the TNFAIP3 locus to ulcerative colitis and rheumatoid arthritis. Overall, our results provide a broad resource of chromatin landscape dynamics and highlight the need for large-scale characterization of effects of genetic variation in stimulated cells.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted September 05, 2018.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Landscape of stimulation-responsive chromatin across diverse human immune cells
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Landscape of stimulation-responsive chromatin across diverse human immune cells
Diego Calderon, Michelle L.T. Nguyen, Anja Mezger, Arwa Kathiria, Vinh Nguyen, Ninnia Lescano, Beijing Wu, John Trombetta, Jessica V. Ribado, David A. Knowles, Ziyue Gao, Audrey V. Parent, Trevor D. Burt, Mark S. Anderson, Lindsey A. Criswell, William J. Greenleaf, Alexander Marson, Jonathan K. Pritchard
bioRxiv 409722; doi: https://doi.org/10.1101/409722
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Landscape of stimulation-responsive chromatin across diverse human immune cells
Diego Calderon, Michelle L.T. Nguyen, Anja Mezger, Arwa Kathiria, Vinh Nguyen, Ninnia Lescano, Beijing Wu, John Trombetta, Jessica V. Ribado, David A. Knowles, Ziyue Gao, Audrey V. Parent, Trevor D. Burt, Mark S. Anderson, Lindsey A. Criswell, William J. Greenleaf, Alexander Marson, Jonathan K. Pritchard
bioRxiv 409722; doi: https://doi.org/10.1101/409722

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (999)
  • Biochemistry (1493)
  • Bioengineering (946)
  • Bioinformatics (6831)
  • Biophysics (2429)
  • Cancer Biology (1792)
  • Cell Biology (2530)
  • Clinical Trials (106)
  • Developmental Biology (1700)
  • Ecology (2576)
  • Epidemiology (1496)
  • Evolutionary Biology (5029)
  • Genetics (3623)
  • Genomics (4638)
  • Immunology (1175)
  • Microbiology (4252)
  • Molecular Biology (1629)
  • Neuroscience (10801)
  • Paleontology (83)
  • Pathology (240)
  • Pharmacology and Toxicology (409)
  • Physiology (555)
  • Plant Biology (1459)
  • Scientific Communication and Education (412)
  • Synthetic Biology (542)
  • Systems Biology (1878)
  • Zoology (260)