The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation
The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation
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BAF和PRC2复合体亚基dpf2和eed拮抗地聚集在tbx3上以控制ESC分化
DOI：
10.1016/j.stem.2018.12.001
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发表时间：
2019-01-03
期刊：
影响因子：
23.9
通讯作者：
Plath, Kathrin
中科院分区：
文献类型：
--
作者：
Zhang, Wensheng;Chronis, Constantinos;Plath, Kathrin
BAF复合物由不同的亚基组成，具有不同的功能和发育作用，尽管许多亚基尚未深入研究。在这里，我们表明Baf45亚基Dpf2保持多能性和ESC分化潜力。Dpf2与Oct4、Sox 2、p300和BAF亚基Brg 1共同占据增强子，缺失Dpf2会干扰ESC的自我更新，诱导Tbx 3的抑制，并损害中内胚层分化，而不会显著改变Brg 1的定位。中内胚层分化可以通过恢复Tbx3的表达来挽救，其远端增强子受到Dpf2依赖性H3K27ac维持和多能性TF和Brg1募集的正调控。相反，PRC2亚基Eed结合基因内Tbx3增强子，以对抗Dpf2依赖性Tbx3表达和中内胚层分化。PRC2亚基Ezh2同样通过涉及Nanog抑制的独特机制对抗Dpf2依赖性分化。总之，这些发现描绘了不同的机制作用，特定的BAF和PRC2亚基在ESC分化。
BAF complexes are composed of different subunits with varying functional and developmental roles, although many subunits have not been examined in depth. Here we show that the Baf45 subunit Dpf2 maintains pluripotency and ESC differentiation potential. Dpf2 co-occupies enhancers with Oct4, Sox2, p300, and the BAF subunit Brg1, and deleting Dpf2 perturbs ESC self-renewal, induces repression of Tbx3, and impairs mesendodermal differentiation withoutdramatically altering Brg1 localization. Mesendodermal differentiation can be rescued by restoring Tbx3 expression, whose distal enhancer is positively regulated by Dpf2-dependent H3K27ac maintenance and recruitment of pluripotency TFs and Brg1. In contrast, the PRC2 subunit Eed binds an intragenic Tbx3 enhancer to oppose Dpf2-dependent Tbx3 expression and mesendodermal differentiation. The PRC2 subunit Ezh2 likewise opposes Dpf2-dependent differentiation through a distinct mechanism involving Nanog repression. Together, these findings delineate distinct mechanistic roles for specific BAF and PRC2 subunits during ESC differentiation.