Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry
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Braveheart, a long noncoding RNA required for cardiovascular lineage commitment

Cell. 2013 Jan 31;152(3):570-83

Authors/Editors: Klattenhoff CA
Scheuermann JC
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
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.

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