IRENEs: new players in the epigenetic control of Nkx2-5 in the heart

Epigenetic control of gene expression is a critical factor during cardiac hypertrophy and failure. Long non-coding RNAs (lncRNAs) are a class of molecules that govern a large range of functions and play an important role during organogenesis and in disease onset. Since they have a specific spatio-temporal expression, their characterization could allow for a better understanding of cardiovascular development and the epigenetic modifications that occur during heart failure, thus enabling them to be promising targets for new therapeutic strategies. Using a bioinformatic approach, we identified not annotated lncRNAs enriched in the heart using RNA sequencing obtained from human induced pluripotent stem cell-derived cardiomyocytes (iPSCs) throughout differentiation. We choose two transcripts upstream of the Nkx2-5 transcription factor. We first validated the potential coding region through PCR and qRT-PCR. We investigated their expression during mouse heart development and in a cardiac hypertrophy model. Furthermore, we performed chromatin epigenetic mapping of the genomic region in order to determine the chromatin and transcriptional state. We observe a correlation between the genomic regulatory region (promoter and enhancer) and the transcriptional state of the lncRNA locus. Preliminary results indicate a crucial role of IRENEs in transcription and chromatin state regulation, suggesting a potential new player in cardiac formation and response to heart failure.