Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment

• Published in: Cell 2013-01, Vol.152 (3), p.570-583
• Main Authors: Klattenhoff, Carla A., Scheuermann, Johanna C., Surface, Lauren E., Bradley, Robert K., Fields, Paul A., Steinhauser, Matthew L., Ding, Huiming, Butty, Vincent L., Torrey, Lillian, Haas, Simon, Abo, Ryan, Tabebordbar, Mohammadsharif, Lee, Richard T., Burge, Christopher B., Boyer, Laurie A.
• Format: Article
• Language: English
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; cardiomyocytes; Cell Differentiation; embryonic stem cells; Embryonic Stem Cells - metabolism; epigenetics; Gene Regulatory Networks; genes; Humans; Mesoderm - cytology; Mesoderm - metabolism; Mice; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; non-coding RNA; Polycomb Repressive Complex 2 - metabolism; Rats; RNA, Long Noncoding
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2013.01.003

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. [Display omitted] ► Braveheart (Bvht) is a heart-associated long noncoding RNA in the mouse ► In embryonic stem cells, Bvht is necessary for cardiovascular lineage commitment ► Bvht functions upstream of MesP1 to regulate a core cardiac gene network ► Bvht interacts with PRC2 to mediate epigenetic activation of the cardiac program Braveheart (Bvht) is a heart-associated long noncoding RNA that is necessary for cardiovascular lineage commitment in embryonic stem cells. Its interaction with the polycomb complex suggests that it may regulate the cardiac program epigenetically.