A Linc1405/Eomes Complex Promotes Cardiac Mesoderm Specification and Cardiogenesis

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

doi:10.1016/j.stem.2018.04.013

A Linc1405/Eomes Complex Promotes Cardiac Mesoderm Specification and Cardiogenesis

Cell Stem Cell. 2018 Jun 1;22(6):893-908.e6. doi: 10.1016/j.stem.2018.04.013. Epub 2018 May 10.

Authors

Xudong Guo¹, Yanxin Xu², Zikang Wang², Yukang Wu², Jiayu Chen³, Guiying Wang², Chenqi Lu⁴, Wenwen Jia², Jiajie Xi², Songcheng Zhu², Zeyidan Jiapaer², Xiaoping Wan⁵, Zhongmin Liu⁶, Shaorong Gao³, Jiuhong Kang⁷

Affiliations

¹ Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Institute of Regenerative Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
² Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
³ Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
⁴ Department of Biostatistics and Computational Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
⁵ Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China.
⁶ Institute of Regenerative Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
⁷ Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: jhkang@tongji.edu.cn.

PMID: 29754779
DOI: 10.1016/j.stem.2018.04.013

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.

Keywords: Eomes; cardiac differentiation; enhancer; epigenetic regulation; lincRNA.

MeSH terms

Animals
Cell Differentiation
Epigenesis, Genetic / genetics
HEK293 Cells
Humans
Mesoderm / cytology
Mesoderm / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocytes, Cardiac / cytology
Myocytes, Cardiac / metabolism*
NIH 3T3 Cells
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*

Substances

RNA, Long Noncoding