Details

Autor(en) / Beteiligte

• 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.

Titel

Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment

Ist Teil von

• Cell, 2013-01, Vol.152 (3), p.570-583

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.