From the Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, University of Frankfurt, Frankfurt, Germany.
Circ Res. 2013 Sep 13;113(7):856-62. doi: 10.1161/CIRCRESAHA.113.302035. Epub 2013 Jul 15.
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.
H3K27 去甲基酶 Jmjd3 的发育作用尚不清楚,尤其是其在应对上游发育信号时针对靶基因的表观遗传调控作用。
确定 Jmjd3 在中胚层和心血管谱系决定中的作用。
在小鼠胚胎干细胞中敲除 Jmjd3 不会影响多能性和自我更新的维持,但会损害中胚层以及随后的内皮和心脏分化。Jmjd3 减少了 Brachyury 启动子上的 H3K27me3 标记,并促进了β-catenin 的募集,β-catenin 对于 Wnt 信号诱导的中胚层分化至关重要。
这些数据表明,Jmjd3 对于中胚层分化和心血管谱系决定是必需的。