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Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment

2013; Cell Press; Volume: 152; Issue: 3 Linguagem: Inglês

10.1016/j.cell.2013.01.003

1097-4172

Carla Klattenhoff, Johanna C. Scheuermann, Lauren E. Surface, Robert K. Bradley, Paul Fields, Matthew L. Steinhauser, Huiming Ding, Vincent L. Butty, Lillian Torrey, Simon Haas, Ryan Abo, Mohammadsharif Tabebordbar, Richard Lee, Christopher B. Burge, Laurie A. Boyer,

RNA Research and Splicing

Long 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.