Braveheart, a long noncoding RNA required for cardiovascular lineage commitment.
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.
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Carla A
CA
Klattenhoff
Johanna C
JC
Scheuermann
Lauren E
LE
Surface
Robert K
RK
Bradley
Paul A
PA
Fields
Matthew L
ML
Steinhauser
Huiming
H
Ding
Vincent L
VL
Butty
Lillian
L
Torrey
Simon
S
Haas
Ryan
R
Abo
Mohammadsharif
M
Tabebordbar
Richard T
RT
Lee
Christopher B
CB
Burge
Laurie A
LA
Boyer
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D062085:RNA, Long Noncoding; D051381:Rats
D051792:Basic Helix-Loop-Helix Proteins; D063151:Polycomb Repressive Complex 2; D062085:RNA, Long Noncoding; C101538:Mesp1 protein, mouse; C494163:Suz12 protein, mouse