Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells.

The developmental role of the H3K27 demethylases Jmjd3, especially its epigenetic regulation at target genes in response to upstream developmental signaling, is unclear. To determine the role of Jmjd3 during mesoderm and cardiovascular lineage commitment. Ablation of Jmjd3 in mouse embryonic stem cells does not affect the maintenance of pluripotency and self-renewal but compromised mesoderm and subsequent endothelial and cardiac differentiation. Jmjd3 reduces H3K27me3 marks at the Brachyury promoter and facilitates the recruitment of β-catenin, which is critical for Wnt signal-induced mesoderm differentiation. These data demonstrate that Jmjd3 is required for mesoderm differentiation and cardiovascular lineage commitment.