Please use this identifier to cite or link to this item: doi:10.22028/D291-31057
Title: Epigenetic Regulation of Alternative mRNA Splicing in Dilated Cardiomyopathy
Author(s): Gi, Weng-Tein
Haas, Jan
Sedaghat-Hamedani, Farbod
Kayvanpour, Elham
Tappu, Rewati
Lehmann, David Hermann
Shirvani Samani, Omid
Wisdom, Michael
Keller, Andreas
Katus, Hugo A.
Meder, Benjamin
Language: English
Title: Journal of Clinical Medicine
Volume: 9
Issue: 5
Publisher/Platform: MDPI
Year of Publication: 2020
Free key words: dilated cardiomyopathy
DNA methylation
alternative splicing
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: In recent years, the genetic architecture of dilated cardiomyopathy (DCM) has been more thoroughly elucidated. However, there is still insufficient knowledge on the modifiers and regulatory principles that lead to the failure of myocardial function. The current study investigates the association of epigenome-wide DNA methylation and alternative splicing, both of which are important regulatory principles in DCM. We analyzed screening and replication cohorts of cases and controls and identified distinct transcriptomic patterns in the myocardium that differ significantly, and we identified a strong association of intronic DNA methylation and flanking exons usage (p < 2 × 10−16). By combining differential exon usage (DEU) and differential methylation regions (DMR), we found a significant change of regulation in important sarcomeric and other DCM-associated pathways. Interestingly, inverse regulation of Titin antisense non-coding RNA transcript splicing and DNA methylation of a locus reciprocal to TTN substantiate these findings and indicate an additional role for non-protein-coding transcripts. In summary, this study highlights for the first time the close interrelationship between genetic imprinting by DNA methylation and the transport of this epigenetic information towards the dynamic mRNA splicing landscape. This expands our knowledge of the genome–environment interaction in DCM besides simple gene expression regulation.
DOI of the first publication: 10.3390/jcm9051499
Link to this record: urn:nbn:de:bsz:291--ds-310575
ISSN: 2077-0383
Date of registration: 22-Dec-2020
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Medizinische Biometrie, Epidemiologie und medizinische Informatik
Professorship: M - Keiner Professur zugeordnet
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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