A Linc1405/Eomes Complex Promotes Cardiac Mesoderm Specification and Cardiogenesis
Mice, Knockout
0301 basic medicine
Cell Differentiation
Epigenesis, Genetic
Mesoderm
Mice, Inbred C57BL
Mice
03 medical and health sciences
HEK293 Cells
NIH 3T3 Cells
Animals
Humans
Myocytes, Cardiac
RNA, Long Noncoding
DOI:
10.1016/j.stem.2018.04.013
Publication Date:
2018-05-10T14:44:33Z
AUTHORS (15)
ABSTRACT
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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