[HTML][HTML] Braveheart, a long noncoding RNA required for cardiovascular lineage commitment

CA Klattenhoff, JC Scheuermann, LE Surface… - Cell, 2013 - cell.com
CA Klattenhoff, JC Scheuermann, LE Surface, RK Bradley, PA Fields, ML Steinhauser…
Cell, 2013cell.com
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 …
Summary
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.
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