Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment
Author(s)Klattenhoff, Carla A.; Scheuermann, Johanna C.; Surface, Lauren E.; Bradley, Robert K.; Fields, Paul A.; Steinhauser, Matthew L.; Ding, Huiming; Torrey, Lillian; Haas, Simon; Abo, Ryan; Tabebordbar, Mohammadsharif; Lee, Richard T.; Burge, Christopher B.; Butty, Vincent; Boyer, Laurie; Klattenhoff, Carla A.; Scheuermann, Johanna C.; Surface, Lauren E.; Bradley, Robert K.; Fields, Paul A.; Burge, Christopher B.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of Biology
Klattenhoff, Carla A., Johanna C. Scheuermann, Lauren E. Surface, Robert K. Bradley, Paul A. Fields, Matthew L. Steinhauser, Huiming Ding, et al. “Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment.” Cell 152, no. 3 (January 2013): 570–583.
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