Braveheart, a long noncoding RNA required for cardiovascular lineage commitment
Cell. 2013 Jan 31;152(3):570-83
Authors/Editors: |
Klattenhoff CA Surface LE Bradley RK Fields PA Steinhauser ML Ding H Butty VL Torrey L Haas S Abo R Tabebordbar M Lee RT Burge CB Boyer LA |
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Publication Date: | 2013 |
Type of Publication: | Journal Article |
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.