Jmjd3 Controls Mesodermal and Cardiovascular Differentiation of Embryonic Stem Cells

RATIONALE:The developmental role of the H3K27 demethylases Jmjd3, especially its epigenetic regulation at target genes in response to upstream developmental signaling, is unclear. OBJECTIVE:To determine the role of Jmjd3 during mesoderm and cardiovascular lineage commitment. METHODS AND RESULTS: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. CONCLUSIONS:These data demonstrate that Jmjd3 is required for mesoderm differentiation and cardiovascular lineage commitment.