Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment

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• 作者：Carla A. Klattenhoff¹ ; ⁶ ; Johanna C. Scheuermann¹ ; ⁶ ; Lauren E. Surface¹ ; Robert K. Bradley¹ ; ² ; ⁷ ; Paul A. Fields¹ ; Matthew L. Steinhauser³ ; Huiming Ding¹ ; Vincent L. Butty¹ ; Lillian Torrey¹ ; Simon Haas¹ ; Ryan Abo¹ ; Mohammadsharif Tabebordbar¹ ; ⁴ ; ⁸ ; Richard T. Lee³ ; ⁵ ; Christopher B. Burge¹ ; ² ; Laurie A. Boyer¹ ; ^{lboyer@mit.edu}
• 刊名：Cell
• 出版年：2013
• 出版时间：31 January, 2013
• 年：2013
• 卷：152
• 期：3
• 页码：570-583
• 全文大小：1895 K

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Summary

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.