TY - JOUR T1 - LSC - 2021 - COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA1794 VL - 58 IS - suppl 65 SP - PA1794 AU - Nemani Sai Sneha Priya 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 Kopp AU - Markus Weckmann Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA1794.abstract N2 - Background: Several environmental exposures like rhinovirus infections alter DNA methylation in airway cells which presents a mechanism through which risk to airflow inflammation and obstruction is posed. Collagen type 4 alpha 3 (COL4A3) is a basal membrane constituent and has anti-angiogenic and anti-inflammatory properties in asthma. COL4A3 is reduced in asthmatic airways. However, the mechanism underlying COL4A3 reduction has remained elusive to date.Objective: To investigate whether ZNF263 binding and an intronic methylation regulate COL4A3 expression in asthmatic epithelium.Methods: RNA and DNA from bronchial biopsies (BB) of 76 asthmatics, 83 controls and from BEAS-2Bs infected with rhinovirus-16 (RV-16) were isolated (AllPrep DNA/RNA kit, Qiagen) and subjected to RNA-sequencing (HiSeq 2500 system, Illumina) and DNA methylation (450k BeadChip, Illumina) analysis. Zinc finger protein (ZNF) 263 binding was assessed by quantitative chromatin immunoprecipitation. Methylation was quantified by pyrosequencing (PyroMark Q24 system, Qiagen). ZNF263 was silenced (ZNF263 On-Target siRNA, Dharmacon technologies) and COL4A3 expression was measured by qPCR.Results: In asthmatic BBs, COL4A3 expression was significantly decreased (pCOL4A3 expression (-60%, pCOL4A3 expression (-40%, p.Conclusion: Our data suggests an epigenetic modification at cg11797365 interrupts ZNF263 binding which may contribute to the COL4A3 expression deficit in asthmatic airways.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA1794.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -