PT - JOURNAL ARTICLE AU - Sai Sneha Priya Nemani AU - Cornelis Joseph Vermeulen AU - Martin Pech AU - Alen Faiz AU - Brian George G. Oliver AU - Maarten van den Berge AU - Janette Kay Burgess AU - Matthias V. Kopp AU - Markus Weckmann TI - <em>COL4A3</em> expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding AID - 10.1183/23120541.00802-2020 DP - 2021 Jan 01 TA - ERJ Open Research PG - 00802-2020 4099 - http://openres.ersjournals.com/content/early/2021/03/18/23120541.00802-2020.short 4100 - http://openres.ersjournals.com/content/early/2021/03/18/23120541.00802-2020.full AB - Background Reduction of COL4A3 in asthmatic airways, one of the six isoforms of collagen 4 results in increased inflammation and angiogenesis implicating it as a central part of asthma pathogenesis. However, the path underlying these diminished COL4A3 levels has been elusive to date. This study investigated a possible mechanism underlying the reduction of COL4A3 expression.Methods Bronchial biopsies of n=76 asthmatics and n=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 ChiP-Seq coupled with qPCR. Effects of ZNF263 silencing, using siRNA, on the COL4A3 expression were studied by 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 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 indicates an epigenetic modification as a contributing factor for the loss of COL4A3 expression in asthmatic airway epithelium.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Nemani has nothing to disclose.Conflict of interest: Dr. Vermeulen has nothing to disclose.Conflict of interest: Dr. Pech has nothing to disclose.Conflict of interest: Dr. Faiz has nothing to disclose.Conflict of interest: Dr. Oliver has nothing to disclose.Conflict of interest: Dr. van den Berge reports grants paid to University from GlaxoSmithKline, Astra Zeneca, Genentech, outside the submitted work.Conflict of interest: Dr. Burgess reports grants from National Health and Medical Research Council, Australia, grants from University of Groningen, grants from European Union, during the conduct of the study; .Conflict of interest: Dr. Kopp reports grants from Federal Ministry of Research and Education (BMBF), during the conduct of the study; personal fees from ALK-Abello, personal fees from Allergopharma, personal fees from Boehringer-Ingelheim, personal fees from Chiesi, personal fees from Glaxo, personal fees from Infectopharm, personal fees from Meda, personal fees from Sanofi-Aventis, personal fees from Leti Pharma, personal fees from Novartis, personal fees from Vertex, outside the submitted work; .Conflict of interest: Dr. Weckmann reports grants from Federal Ministry for Education and Research (BMBF), grants from University of Luebeck, grants from German Academic Exchange Service, during the conduct of the study; .