Braveheart, a long noncoding RNA required for cardiovascular lineage commitment

Cell. 2013 Jan 31;152(3):570-83. doi: 10.1016/j.cell.2013.01.003. Epub 2013 Jan 24.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation*
  • Embryonic Stem Cells / metabolism*
  • Gene Regulatory Networks
  • Humans
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Polycomb Repressive Complex 2 / metabolism
  • RNA, Long Noncoding*
  • Rats

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Mesp1 protein, mouse
  • RNA, Long Noncoding
  • Suz12 protein, mouse
  • Polycomb Repressive Complex 2

Associated data

  • GEO/GSE39656