Project description:Very little information is available about non-coding(nc)RNAs and their role in regulating tissue responses in myocardial ischemia and acute infarction. We measured for the first time nascent RNA transcription of protein coding genes, primary(pri)-miRNAs, long non-coding(lnc)RNAs and enhancer(e)RNAs in healthy myocardium, border zone to ischemia and infarction area in pig hearts using GRO-seq. The gene expression analysis indicated a gradient of induction of inflammatory mediators, and repression of PPAR-signaling and oxidative phosphorylation. An exception to rule was A1 adenosine receptor, which exhibited induced gene expression in the border zone, where it might increase myocardial resistance to ischemia, but repression in the ischemic zone. In addition, we interrogated for the first time the transcriptional regulation of pri-miRs and provide evidence that several arrhythmia-related target genes are further repressed at post-transcriptional level. We identified 450 lncRNAs which were differently regulated by ischemia including novel lncRNAs expressed in antisense orientation to major myocardial transcription factors GATA4, GATA6 and KLF6. Finally, characterization of enhancers exhibiting differential expression of eRNAs, pointed a central role for KLF, MEF2C, ETS, NFY, ATF, E2F2 and NRF1 transcription factors in determining tissue-specific responses to ischemic insult. In conclusion, GRO-Seq allowed us to follow the gradient of gene expression occurring in the ischemic heart and identify novel ncRNAs regulated by oxygen deprivation. These findings have identified potential new targets for diagnosis and treatment of myocardial ischemia based on acute changes in eRNA, lncRNA and miRNA expression in the affected heart.
Project description:We systematically identified, annotated and characterised the mouse long non-coding transcriptome during myocardial infarction, revealing hundreds of novel heart specific lncRNAs with unique functional and regulatory characteristics. 2 conditions, 4 biological replicates per condition
Project description:We systematically identified, annotated and characterised the mouse long non-coding transcriptome during myocardial infarction, revealing hundreds of novel heart specific lncRNAs with unique functional and regulatory characteristics.