COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding.

Nemani, SSP; Vermeulen, CJ; Pech, M; Faiz, A; Oliver, BGG; van den Berge, M; Burgess, JK; Kopp, MV; Weckmann, M

COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding.

Nemani, SSP Vermeulen, CJ Pech, M Faiz, A

Oliver, BGG van den Berge, M Burgess, JK Kopp, MV Weckmann, M

Permalink

Publisher:: European Respiratory Society (ERS)
Publication Type:: Journal Article
Citation:: ERJ Open Research, 2021, 7, (2), pp. 00802-02020
Issue Date:: 2021-04-15

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download full textAdobe PDF (870.77 kB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Nemani, SSP
dc.contributor.author	Vermeulen, CJ
dc.contributor.author	Pech, M
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Oliver, BGG
dc.contributor.author	van den Berge, M
dc.contributor.author	Burgess, JK
dc.contributor.author	Kopp, MV
dc.contributor.author	Weckmann, M
dc.date.accessioned	2022-01-14T04:56:04Z
dc.date.available	2021-03-18
dc.date.available	2022-01-14T04:56:04Z
dc.date.issued	2021-04-15
dc.identifier.citation	ERJ Open Research, 2021, 7, (2), pp. 00802-02020
dc.identifier.issn	2312-0541
dc.identifier.issn	2312-0541
dc.identifier.uri	http://hdl.handle.net/10453/153116
dc.description.abstract	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.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	European Respiratory Society (ERS)
dc.relation.ispartof	ERJ Open Research
dc.relation.isbasedon	10.1183/23120541.00802-2020
dc.rights	info:eu-repo/semantics/openAccess
dc.title	COL4A3 expression in asthmatic epithelium depends on intronic methylation and ZNF263 binding.
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-01-14T04:56:02Z
pubs.issue	2
pubs.publication-status	Published online
pubs.volume	7
utslib.citation.issue	2

Abstract:

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/153116