GSTCD and INTS12 regulation and expression in the human lung
Genome-Wide Association Study (GWAS) meta-analyses have identified a strong association signal for lung function, which maps to a region on 4q24 containing two oppositely transcribed genes: glutathione S-transferase, C-terminal domain containing (GSTCD) and integrator complex subunit 12 (INTS12). Bo...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science
2013
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| Online Access: | https://eprints.nottingham.ac.uk/2687/ |
| _version_ | 1848790849790410752 |
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| author | Obeidat, Ma’en Miller, Suzanne Probert, Kelly Billington, Charlotte K. Henry, Amanda P. Hodge, Emily Nelson, Carl P. Stewart, Ceri E. Swan, Caroline Wain, Louise V. Soler Artigas, María Melén, Erik Ushey, Kevin Hao, Ke Lamontagne, Maxime Bossé, Yohan Postma, Dirkje S. Tobin, Martin D. Sayers, Ian Hall, Ian P. |
| author_facet | Obeidat, Ma’en Miller, Suzanne Probert, Kelly Billington, Charlotte K. Henry, Amanda P. Hodge, Emily Nelson, Carl P. Stewart, Ceri E. Swan, Caroline Wain, Louise V. Soler Artigas, María Melén, Erik Ushey, Kevin Hao, Ke Lamontagne, Maxime Bossé, Yohan Postma, Dirkje S. Tobin, Martin D. Sayers, Ian Hall, Ian P. |
| author_sort | Obeidat, Ma’en |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Genome-Wide Association Study (GWAS) meta-analyses have identified a strong association signal for lung function, which maps to a region on 4q24 containing two oppositely transcribed genes: glutathione S-transferase, C-terminal domain containing (GSTCD) and integrator complex subunit 12 (INTS12). Both genes were found to be expressed in a range of human airway cell types. The promoter regions and transcription start sites were determined in mRNA from human lung and a novel splice variant was identified for each gene. We obtained the following evidence for GSTCD and INTS12 co-regulation and expression: (i) correlated mRNA expression was observed both via Q-PCR and in a lung expression quantitative trait loci (eQTL) study, (ii) induction of both GSTCD and INTS12 mRNA expression in human airway smooth muscle cells was seen in response to TGFβ1, (iii) a lung eQTL study revealed that both GSTCD and INTS12 mRNA levels positively correlate with percent predicted FEV1, and (iv) FEV1 GWAS associated SNPs in 4q24 were found to act as an eQTL for INTS12 in a number of tissues. In fixed sections of human lung tissue, GSTCD protein expression was ubiquitous, whereas INTS12 expression was predominantly in epithelial cells and pneumocytes. During human fetal lung development, GSTCD protein expression was observed to be highest at the earlier pseudoglandular stage (10-12 weeks) compared with the later canalicular stage (17-19 weeks), whereas INTS12 expression levels did not alter throughout these stages. Knowledge of the transcriptional and translational regulation and expression of GSTCD and INTS12 provides important insights into the potential role of these genes in determining lung function. Future work is warranted to fully define the functions of INTS12 and GSTCD. |
| first_indexed | 2025-11-14T18:19:09Z |
| format | Article |
| id | nottingham-2687 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:19:09Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-26872020-05-04T16:38:51Z https://eprints.nottingham.ac.uk/2687/ GSTCD and INTS12 regulation and expression in the human lung Obeidat, Ma’en Miller, Suzanne Probert, Kelly Billington, Charlotte K. Henry, Amanda P. Hodge, Emily Nelson, Carl P. Stewart, Ceri E. Swan, Caroline Wain, Louise V. Soler Artigas, María Melén, Erik Ushey, Kevin Hao, Ke Lamontagne, Maxime Bossé, Yohan Postma, Dirkje S. Tobin, Martin D. Sayers, Ian Hall, Ian P. Genome-Wide Association Study (GWAS) meta-analyses have identified a strong association signal for lung function, which maps to a region on 4q24 containing two oppositely transcribed genes: glutathione S-transferase, C-terminal domain containing (GSTCD) and integrator complex subunit 12 (INTS12). Both genes were found to be expressed in a range of human airway cell types. The promoter regions and transcription start sites were determined in mRNA from human lung and a novel splice variant was identified for each gene. We obtained the following evidence for GSTCD and INTS12 co-regulation and expression: (i) correlated mRNA expression was observed both via Q-PCR and in a lung expression quantitative trait loci (eQTL) study, (ii) induction of both GSTCD and INTS12 mRNA expression in human airway smooth muscle cells was seen in response to TGFβ1, (iii) a lung eQTL study revealed that both GSTCD and INTS12 mRNA levels positively correlate with percent predicted FEV1, and (iv) FEV1 GWAS associated SNPs in 4q24 were found to act as an eQTL for INTS12 in a number of tissues. In fixed sections of human lung tissue, GSTCD protein expression was ubiquitous, whereas INTS12 expression was predominantly in epithelial cells and pneumocytes. During human fetal lung development, GSTCD protein expression was observed to be highest at the earlier pseudoglandular stage (10-12 weeks) compared with the later canalicular stage (17-19 weeks), whereas INTS12 expression levels did not alter throughout these stages. Knowledge of the transcriptional and translational regulation and expression of GSTCD and INTS12 provides important insights into the potential role of these genes in determining lung function. Future work is warranted to fully define the functions of INTS12 and GSTCD. Public Library of Science 2013-09-18 Article PeerReviewed Obeidat, Ma’en, Miller, Suzanne, Probert, Kelly, Billington, Charlotte K., Henry, Amanda P., Hodge, Emily, Nelson, Carl P., Stewart, Ceri E., Swan, Caroline, Wain, Louise V., Soler Artigas, María, Melén, Erik, Ushey, Kevin, Hao, Ke, Lamontagne, Maxime, Bossé, Yohan, Postma, Dirkje S., Tobin, Martin D., Sayers, Ian and Hall, Ian P. (2013) GSTCD and INTS12 regulation and expression in the human lung. PLoS ONE, 8 (9). e74630/1-e74630/16. ISSN 1932-6203 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074630 doi:10.1371/journal.pone.0074630 doi:10.1371/journal.pone.0074630 |
| spellingShingle | Obeidat, Ma’en Miller, Suzanne Probert, Kelly Billington, Charlotte K. Henry, Amanda P. Hodge, Emily Nelson, Carl P. Stewart, Ceri E. Swan, Caroline Wain, Louise V. Soler Artigas, María Melén, Erik Ushey, Kevin Hao, Ke Lamontagne, Maxime Bossé, Yohan Postma, Dirkje S. Tobin, Martin D. Sayers, Ian Hall, Ian P. GSTCD and INTS12 regulation and expression in the human lung |
| title | GSTCD and INTS12 regulation and expression in the human lung |
| title_full | GSTCD and INTS12 regulation and expression in the human lung |
| title_fullStr | GSTCD and INTS12 regulation and expression in the human lung |
| title_full_unstemmed | GSTCD and INTS12 regulation and expression in the human lung |
| title_short | GSTCD and INTS12 regulation and expression in the human lung |
| title_sort | gstcd and ints12 regulation and expression in the human lung |
| url | https://eprints.nottingham.ac.uk/2687/ https://eprints.nottingham.ac.uk/2687/ https://eprints.nottingham.ac.uk/2687/ |