A Linc1405/Eomes Complex Promotes Cardiac Mesoderm Specification and Cardiogenesis

Publication date: Available online 10 May 2018
Source:Cell Stem Cell
Author(s): Xudong Guo, Yanxin Xu, Zikang Wang, Yukang Wu, Jiayu Chen, Guiying Wang, Chenqi Lu, Wenwen Jia, Jiajie Xi, Songcheng Zhu, Zeyidan Jiapaer, Xiaoping Wan, Zhongmin Liu, Shaorong Gao, Jiuhong Kang
Large intergenic non-coding RNAs (lincRNAs) play widespread roles in epigenetic regulation during multiple differentiation processes, but little is known about their mode of action in cardiac differentiation. Here, we identified the key roles of a lincRNA, termed linc1405, in modulating the core network of cardiac differentiation by functionally interacting with Eomes. Chromatin- and RNA-immunoprecipitation assays showed that exon 2 of linc1405 physically mediates a complex consisting of Eomes, trithorax group (TrxG) subunit WDR5, and histone acetyltransferase GCN5 binding at the enhancer region of Mesp1 gene and activates its expression during cardiac mesoderm specification of embryonic stem cells. Importantly, linc1405 co-localizes with Eomes, WDR5, and GCN5 at the primitive streak, and linc1405 depletion impairs heart development and function in vivo. In summary, linc1405 mediates a Eomes/WDR5/GCN5 complex that contributes to cardiogenesis, highlighting the critical roles of lincRNA-based complexes in the epigenetic regulation of cardiogenesis in vitro and in vivo.

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Teaser

Kang and colleagues identify linc1405 as a crucial regulator of cardiac differentiation via its interaction with Eomes. Linc1405 mediates an Eomes/WDR5/GCN5 regulatory complex at the Mesp1 enhancer, which coordinates Mesp1 expression and cardiac specification. They also show that linc1405 depletion results in impaired heart development and function in vivo.


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