Klattenhoff, Carla A.Scheuermann, Johanna C.Surface, Lauren E.Bradley, Robert K.Fields, Paul A.Steinhauser, MatthewDing, HuimingButty, Vincent L.Torrey, LillianHaas, SimonAbo, RyanTabebordbar, MLee, RichardBurge, Christopher B.Boyer, Laurie A.2014-12-152013Klattenhoff, Carla A., Johanna C. Scheuermann, Lauren E. Surface, Robert K. Bradley, Paul A. Fields, Matthew L. Steinhauser, Huiming Ding, et al. 2013. “Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment.” Cell 152 (3) (January): 570–583.0092-8674http://nrs.harvard.edu/urn-3:HUL.InstRepos:13515594Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor. We also show that Bvht interacts with SUZ12, a component of polycomb-repressive complex 2 (PRC2), during cardiomyocyte differentiation, suggesting that Bvht mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development.en-USJournal Article10.1016/j.cell.2013.01.003