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.
Keywords: Brachyury protein; Jmjd3 protein, mouse; Wnt signaling pathway; embryonic stem cells; epigenomics; mesoderm.