RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response. (December 2016)

• Record Type: Journal Article
• Authors: Prunotto, Andrea; Stevenson, Brian; Berthonneche, Corinne; Schüpfer, Fanny; Beckmann, Jacques; Maurer, Fabienne; Bergmann, Sven
• Is Part Of: BMC genomics. Volume 17:Number 1(2016)
• Page Start: 1
• Page End: 14
• Publication Date: 2016-12
• Subjects: Mouse heart -- β-adrenergic system -- Cardiac hypertrophy -- RNAseq -- Atenolol -- Isoproterenol; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-016-3059-6
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with theβ -blocker atenolol (ATE) and theβ -agonist isoproterenol (ISO). Results Differential expression analyses revealed a large set of genes responding to ISO (n = 1770 atFDR = 0.0001) and a comparatively small one responding to ATE (n = 23 atFDR = 0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation ofr = −0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibit coherent transcription profiles across some strains and/or treatments. Correlations between these modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Conclusions Our study provides new insights into the transcriptional response of the heart to perturbations of theβ -adrenergic system, implicating several new genes that had not been associated to this system previously.