RT Journal Article SR Electronic T1 COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding JF ERJ Open Research JO erjor FD European Respiratory Society SP 00802-2020 DO 10.1183/23120541.00802-2020 VO 7 IS 2 A1 Sai Sneha Priya Nemani A1 Cornelis Joseph Vermeulen A1 Martin Pech A1 Alen Faiz A1 Brian George G. Oliver A1 Maarten van den Berge A1 Janette Kay Burgess A1 Matthias V. Kopp A1 Markus Weckmann YR 2021 UL http://openres.ersjournals.com/content/7/2/00802-2020.abstract AB Background Reduction of COL4A3, one of the six isoforms of collagen 4, in asthmatic airways results in increased inflammation and angiogenesis, implicating it as a central part of asthma pathogenesis. However, to date, the path underlying these diminished COL4A3 levels has been elusive. This study investigated a possible mechanism underlying the reduction of COL4A3 expression.Methods Bronchial biopsies of 76 patients with asthma and 83 controls were subjected to RNA-sequencing and DNA methylation bead arrays to identify expression and methylation changes. The binding of ZNF263 was analysed by chromatin-immunoprecipitation sequencing coupled with quantitative (q)PCR. Effects of ZNF263 silencing, using small interfering RNA, on the COL4A3 expression were studied using qPCR.Results COL4A3 expression was significantly reduced in bronchial biopsies compared to healthy controls, whereas DNA methylation levels at cg11797365 were increased. COL4A3 expression levels were significantly low in asthmatics without inhaled corticosteroid (ICS) use, whereas the expression was not statistically different between asthmatics using ICS and controls. Methylation levels at cg11797365 in vitro were increased upon consecutive rhinovirus infections.Conclusion Our data indicate an epigenetic modification as a contributing factor for the loss of COL4A3 expression in asthmatic airway epithelium.An epigenetic modification interrupts ZNF263 binding, which may contribute to the loss of COL4A3 expression in asthmatic airway epithelium https://bit.ly/39cZbyn