Details zur Publikation |
| Kategorie | Textpublikation |
| Referenztyp | Zeitschriften |
| DOI | 10.1111/all.15658 |
| Lizenz |
|
| Titel (primär) | Global hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions |
| Autor | Thürmann, L.; Klös, M.; Mackowiak, S.D.; Bieg, M.; Bauer, T.; Ishaque, N.; Messingschlager, M.; Herrmann, C.; Röder, S.; Bauer, M.; Schäuble, S.; Faessler, E.; Hahn, U.; Weichenhan, D.; Mücke, O.; Plass, C.; Borte, M.; von Mutius, E.; Stangl, G.I.; Lauener, R.; Karvonen, A.M.; Divaret-Chauveau, A.; Riedler, J.; Heinrich, J.; Standl, M.; von Berg, A.; Schaaf, B.; Herberth, G.
; Kabesch, M.; Eils, R.; Trump, S.; Lehmann, I. |
| Journal / Serie | Allergy |
| Erscheinungsjahr | 2023 |
| Department | IMMU |
| Sprache | englisch |
| Topic | T9 Healthy Planet |
| Supplements | https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0001-FigureS1.pdf https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0002-FigureS2.pdf https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0003-FigureS3.pdf https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0004-FigureS4.pdf https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0005-FigureS5.pdf https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0006-FigureS6.pdf https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0007-Supinfo.docx https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fall.15658&file=all15658-sup-0008-Supinfo.xlsx |
| Keywords | asthma; cord blood; DNA-methylation; prenatal exposure |
| Abstract |
Childhood asthma is a result of a complex interaction of
genetic and environmental components causing epigenetic and immune
dysregulation, airway inflammation and impaired lung function. Although
different microarray based EWAS studies have been conducted, the impact
of epigenetic regulation in asthma development is still widely unknown.
We have therefore applied unbiased whole genome bisulfite sequencing
(WGBS) to characterize global DNA-methylation profiles of asthmatic
children compared to healthy controls. Peripheral blood samples of 40 asthmatic and 42 control
children aged 5-15 years from three birth cohorts were sequenced
together with paired cord blood samples. Identified differentially
methylated regions (DMRs) were categorized in genotype-associated,
cell-type-dependent, or prenatally-primed. Network analysis and
subsequent natural language processing of DMR-associated genes was
complemented by targeted analysis of functional translation of
epigenetic regulation on the transcriptional and protein level. In total, 158 DMRs were identified in asthmatic children
compared to controls of which 37% were related to the eosinophil
content. A global hypomethylation was identified affecting predominantly
enhancer regions and regulating key immune genes such as IL4, IL5RA, and EPX.
These DMRs were confirmed in n=267 samples and could be linked to
aberrant gene expression. Out of the 158 DMRs identified in the
established phenotype, 56 were perturbed already at birth and linked, at
least in part, to prenatal influences such as tobacco smoke exposure or
phthalate exposure. This is the first epigenetic study based on whole genome
sequencing to identify marked dysregulation of enhancer regions as a
hallmark of childhood asthma. |
| dauerhafte UFZ-Verlinkung | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25073 |
| Thürmann, L., Klös, M., Mackowiak, S.D., Bieg, M., Bauer, T., Ishaque, N., Messingschlager, M., Herrmann, C., Röder, S., Bauer, M., Schäuble, S., Faessler, E., Hahn, U., Weichenhan, D., Mücke, O., Plass, C., Borte, M., von Mutius, E., Stangl, G.I., Lauener, R., Karvonen, A.M., Divaret-Chauveau, A., Riedler, J., Heinrich, J., Standl, M., von Berg, A., Schaaf, B., Herberth, G., Kabesch, M., Eils, R., Trump, S., Lehmann, I. (2023): Global hypomethylation in childhood asthma identified by genome-wide DNA-methylation sequencing preferentially affects enhancer regions Allergy |
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