Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma

Author:

Helling Britney A.ORCID,Sobreira Débora R.,Hansen Grace T.ORCID,Sakabe Noboru J.,Luo Kaixuan,Billstrand Christine,Laxman Bharathi,Nicolae Raluca I.,Nicolae Dan L.,Bochkov Yury A.,Gern James E.ORCID,Nobrega Marcelo A.,White Steven R.,Ober Carole

Abstract

AbstractThere is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n = 9) show different transcriptional and chromatin responses to RV infection compared to those without asthma (n = 9). Both the number and magnitude of transcriptional and chromatin responses to RV were muted in cells from asthma cases compared to controls. Pathway analysis of the transcriptionally responsive genes revealed enrichments of apoptotic pathways in controls but inflammatory pathways in asthma cases. Using promoter capture Hi-C we tethered regions of RV-responsive chromatin to RV-responsive genes and showed enrichment of these regions and genes at asthma GWAS loci. Taken together, our studies indicate a delayed or prolonged inflammatory state in cells from asthma cases and highlight genes that may contribute to genetic risk for asthma.

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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