Microarray-based transcriptome profiling after H19 KO

Treatment of pathological cardiac remodeling and subsequent heart failure represents an unmet clinical need. The well conserved lncRNA H19 shows as powerful therapeutic potential in the treatment of pathological cardiac hypertrophy. H19 is strongly repressed in failing hearts from mice, pigs and humans. Gene therapy using murine but also human H19 strongly attenuated heart failure even when cardiac hypertrophy was already established. Using microarray , GSEA and ChIP-Seq we identified a link between H19 and NFAT signalling. H19 physically interacts with PRC2 to epigenetically induced Tescalcin repression which in turn leads to reduced NFAT expression and activity. RNA was isolated from the cardiomyocyte fractions of H19 knockout mice and corresponding wt littermates generated 6 weeks after TAC (transverse aortic constriction) surgery. RNA quality and quantity was assessed before microarray-based transcriptome profiling. Deregulated mRNAs due to the absence of H19 were analysed by Gene Set Enrichment Analysis GSEA.