Cell (2013) 152, 570–583
Dev Cell (2013) 24, 206–214
Recent articles by Klattenhoff et al (2013) and Grote et al (2013) identify long non-coding RNAs, or lncRNAs, important for specifying the cardiac lineage. Depletion of a lncRNA, aptly named Braveheart, resulted in loss of beating cardiomyocytes during embryonic stem (ES) cell differentiation and failure to activate a key network of cardiac transcription factors. Immunoprecipitation of the protein complex associated with Braveheart revealed that the lncRNA physically interacts with epigenetic machinery that regulates cardiac gene expression. Similarly, a second lncRNA, Fendrr, also interacts with epigenetic regulators to promote proper cardiac gene expression and function in vivo in mice. These studies highlight the importance of lncRNAs during lineage commitment and provide a new layer of regulation involved in determining cardiac cell fate.