Department of Biology, Case Western Reserve University, Cleveland, OH, USA.
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
FEBS Lett. 2022 Jul;596(13):1672-1685. doi: 10.1002/1873-3468.14334. Epub 2022 Mar 27.
Sequential differentiation of presomitic progenitors into myocytes and subsequently into myotubes and myofibers is essential for the myogenic differentiation program (MDP) crucial for muscle development. Signaling factors involved in MDP are polycomb repressive complex 2 (PRC2) targets in various developmental contexts. PRC2 is active in the developing myotomes during MDP, but how it regulates MDP is unclear. Here, we found that myocyte differentiation to myotubes requires Enhancer of Zeste 2 (EZH2), the catalytic component of PRC2. We observed elevated retinoic acid (RA) signaling in the prospective myocytes in the Ezh2 mutants (E8.5-Mus ), and its inhibition can partially rescue the myocyte differentiation defect. Together, our data demonstrate a new role for PRC2-EZH2 during myocyte differentiation into myotubes by modulating RA signaling.
体节前体祖细胞向肌细胞，随后向肌管和肌纤维的顺序分化对于肌肉发育至关重要的肌发生分化程序（MDP）至关重要。MDP 中涉及的信号因子是各种发育背景中多梳抑制复合物 2（PRC2）的靶标。PRC2 在 MDP 期间在发育中的肌节中活跃，但它如何调节 MDP 尚不清楚。在这里，我们发现肌细胞向肌管的分化需要 Enhancer of Zeste 2（EZH2），即 PRC2 的催化成分。我们观察到 Ezh2 突变体（E8.5-Mus）中的预期肌细胞中视黄酸（RA）信号升高，其抑制作用可部分挽救肌细胞分化缺陷。总之，我们的数据表明，PRC2-EZH2 通过调节 RA 信号在肌细胞向肌管分化过程中发挥新的作用。
