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Título: | Asthma-associated genetic variants induce IL33 differential expression through an enhancer-blocking regulatory region |
Autor: | Aneas, Ivy; Decker, Donna C.; Howard, Chanie L.; Sobreira, Débora R.; Sakabe, Noboru J.; Blaine, Kelly M.; Stein, Michelle M.; Hrusch, Cara L.; Montefiori, Lindsey E.; Tena, Juan J. CSIC ORCID; Magnaye, Kevin M.; Clay, Selene M.; Gern, James E.; Jackson, Daniel J.; Altman, Matthew C.; Naureckas, Edward T.; Hogarth, Douglas K.; White, Steven R.; Gómez-Skarmeta, José Luis CSIC ORCID ; Schoetler, Nathan; Ober, Carole; Sperling, Anne I.; Nóbrega, Marcelo A. | Palabras clave: | Gene regulation Genome-wide association studies Interleukins |
Fecha de publicación: | 2021 | Editor: | Nature Publishing Group | Citación: | Nature Communications 12: 6115 (2021) | Resumen: | 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. | Versión del editor: | http://dx.doi.org/10.1038/s41467-021-26347-z | URI: | http://hdl.handle.net/10261/260363 | DOI: | 10.1038/s41467-021-26347-z | E-ISSN: | 2041-1723 |
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Asthma-associated_Aneas_PV_Art2021.pdf | 1,68 MB | Adobe PDF | Visualizar/Abrir |
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