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Transcriptional regulation: deciphering the network

ESC Congress Report

  • “Dark matter” of the genome (long non-coding RNA) may outnumber protein-coding genes and undergoes changes post-MI
  • Upregulation of a calcineurin splice variant reduces infarct size
  • Decreased expression of the AP1 subunit JunD increases oxidative stress in ageing mice
  • MicroRNA targets converge to modulate downstream effectors of pathological cardiac remodeling


View the Slides from this session in ESC Congress 365

This exciting Basic Science session, proposed by the newly formed ESC Scientists of Tomorrow community, probed the regulatory networks that dynamically coordinate gene expression in the developing and diseased heart.

To kick-off, a cutting-edge exploration of the “dark matter” of the genome or long non-coding RNA, that recent estimates suggest may outnumber protein-coding genes, was presented by Samir Ounzain, from the Pedrazzini laboratory in Lausane. We learnt how expression of lncRNAs changes post-MI, and how analysis of linked enhancer sequences and expression profiling suggests candidate roles in remodeling and regeneration.

Post-transciptional regulation remained the topic of the second presentation from Enrique Lara-Pezzi (Madrid) who shared his results on the “alternative” heart: a systematic study of the damaged heart revealed that alternatively spliced genes tend not to be differentially expressed and share specific functional categories. The importance of alternative splicing in pathology was illustrated by the finding that upregulation of a calcineurin splice variant reduces infarct size and promotes vascularization post-MI.

Transcriptional changes in the ageing heart were the focus of Francesco Paneni’s talk (Stockholm), who reported that decreased expression of the AP1 subunit JunD in ageing mice leads to increased oxidative stress and endothelial dysfunction, a phenotype recapitulated in JunD mutant mice.

The final presentation by Eva Van Rooij (Amsterdam), laureat of the 2014 Council on Basic Cardiovascular Science Outstanding Achievement Award, brought us back to RNA mediated post-transcriptional regulation of gene expression in an exposé on “myomiR” microRNAs as regulators of cardiac growth.
Dr Van Rooij showed how multiple direct microRNA targets converge to profoundly modulate downstream effectors of pathological cardiac remodeling.

This concluded an enjoyable series of complementary talks that provided an update on mechanisms regulating gene expression under pathological conditions.

References


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Transcriptional regulation: deciphering the network

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.