Journal
CELL
Volume 152, Issue 3, Pages 570-583Publisher
CELL PRESS
DOI: 10.1016/j.cell.2013.01.003
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Funding
- Damon Runyon Cancer Research Foundation [DRG 2032-09, DFS 04-12]
- NIH [K08 (DK090147)]
- Watkins Cardiovascular Leadership Award
- EMBO long-term fellowship
- NHLBI Bench [U01HL098179, U01HL098188]
- Richard and Susan Smith Family Foundation, Chestnut Hill, MA
- Pew Scholar's Program in the Biomedical Sciences
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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 nascentmesoderm 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 polycombrepressive 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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