Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region

Ivy Aneas (), Donna C. Decker, Chanie L. Howard, Débora R. Sobreira, Noboru J. Sakabe, Kelly M. Blaine, Michelle M. Stein, Cara L. Hrusch, Lindsey E. Montefiori, Juan Tena, Kevin M. Magnaye, Selene M. Clay, James E. Gern, Daniel J. Jackson, Matthew C. Altman, Edward T. Naureckas, Douglas K. Hogarth, Steven R. White, Jose Luis Gomez-Skarmeta, Nathan Schoetler, Carole Ober, Anne I. Sperling () and Marcelo A. Nóbrega ()
Additional contact information
Ivy Aneas: University of Chicago
Donna C. Decker: University of Chicago
Chanie L. Howard: University of Chicago
Débora R. Sobreira: University of Chicago
Noboru J. Sakabe: University of Chicago
Kelly M. Blaine: University of Chicago
Michelle M. Stein: University of Chicago
Cara L. Hrusch: University of Chicago
Lindsey E. Montefiori: University of Chicago
Juan Tena: Universidad Pablo de Olavide
Kevin M. Magnaye: University of Chicago
Selene M. Clay: University of Chicago
James E. Gern: University of Wisconsin School of Medicine and Public Health
Daniel J. Jackson: University of Wisconsin School of Medicine and Public Health
Matthew C. Altman: University of Washington
Edward T. Naureckas: University of Chicago
Douglas K. Hogarth: University of Chicago
Steven R. White: University of Chicago
Jose Luis Gomez-Skarmeta: Universidad Pablo de Olavide
Nathan Schoetler: University of Chicago
Carole Ober: University of Chicago
Anne I. Sperling: University of Chicago
Marcelo A. Nóbrega: University of Chicago

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Genome-wide association studies (GWAS) have implicated the IL33 locus in asthma, but the underlying mechanisms remain unclear. Here, we identify a 5 kb region within the GWAS-defined segment that acts as an enhancer-blocking element in vivo and in vitro. Chromatin conformation capture showed that this 5 kb region loops to the IL33 promoter, potentially regulating its expression. We show that the asthma-associated single nucleotide polymorphism (SNP) rs1888909, located within the 5 kb region, is associated with IL33 gene expression in human airway epithelial cells and IL-33 protein expression in human plasma, potentially through differential binding of OCT-1 (POU2F1) to the asthma-risk allele. Our data demonstrate that asthma-associated variants at the IL33 locus mediate allele-specific regulatory activity and IL33 expression, providing a mechanism through which a regulatory SNP contributes to genetic risk of asthma.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26347-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26347-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26347-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().