Conditional Ablation of Ezh2 in Murine Hearts Reveals Its Essential Roles in Endocardial Cushion Formation, Cardiomyocyte Proliferation and Survival

• DOI: 10.1371/journal.pone.0031005
• Publication Date: 2012-02-01T21:40:29Z
• Authors: Li Chen; Yanlin Ma; Eun Young Kim; Wei Yu; Robert J. Schwartz; Ling Qian; Jun Wang
• Keywords: PRC2; Heart development

Ezh2 is a histone trimethyltransferase that silences genes mainly via catalyzing trimethylation of 3 lysine 27 (H3K27Me3). The role as regulator gene silencing and cell proliferation in cancer development has been extensively investigated; however, its function heart during embryonic cardiogenesis not well studied. In the present study, we used genetically modified mouse system which was specifically ablated heart. We identified wide spectrum cardiovascular malformations mutant mice, collectively led to perinatal death. heart, endocardial cushions (ECs) were hypoplastic endothelial-to-mesenchymal transition (EMT) process impaired. hearts mice also exhibited decreased cardiomyocyte increased apoptosis. further Hey2 gene, important for cardiac morphogenesis, downstream target Ezh2. regulation expression by may be independent Notch signaling activity. Our work defines an indispensible chromatin remodeling factor normal development.