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Stem Cells:研究揭示Pcid2蛋白调控胚胎干细胞多能性维持的机制

  1. Pcid2蛋白
  2. 生物物理所
  3. 胚胎干细胞

来源:生物谷 2014-04-11 20:24

近日,中科院生物物理研究所范祖森课题组研究揭示了Pcid2蛋白调控胚胎干细胞(ES细胞)多能性维持的分子机制。

近日,中科院生物物理研究所范祖森课题组在Stem Cells杂志发表了题为"Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability."的研究论文,揭示了Pcid2蛋白调控胚胎干细胞(ES细胞)多能性维持的分子机制。

范祖森课题组研究发现,Pcid2基因敲除导致人和小鼠ES细胞失去干性,在体内失去三胚层分化能力。并且Pcid2基因敲除导致胚胎不能发育至囊胚期。该课题组进一步证实了Pcid2通过抑制ES细胞分化基因的表达而维持ES细胞的干性。通过酵母双杂交筛选和免疫共沉淀等实验体系,发现CBP/p300乙酰转移酶活抑制因子EID1与Pcid2相互作用,并共存在于CBP/p300复合体中。该课题组进一步研究发现,Pcid2与E3泛素连接酶MDM2竞争性结合EID1,抑制EID1的降解过程,阻断CBP/p300的乙酰转移酶活性和分化相关基因启动子区H3组蛋白Lys9及Lys14位乙酰化修饰,从而抑制ES细胞分化相关基因的表达。综上所述,Pcid2通过调控EID1的蛋白稳定性,抑制人及小鼠ES细胞发育相关基因表达,在ES细胞自我更新与分化的调控中发挥重要作用。该研究为理解ES细胞重编程机制提供了重要依据。 (生物谷Bioon.com)

生物谷推荐的英文摘要:

 

Stem Cells    DOI: 10.1002/stem.1580

Pcid2 Inactivates Developmental Genes in Human and Mouse Embryonic Stem Cells to Sustain Their Pluripotency by Modulation of EID1 Stability

Buqing YE, Zhonghua Dai, Benyu Liu, Rui Wang, Chong Li, Guanling Huang, Shuo Wang, Pengyan Xia, Xuan Yang, Kazuhiko Kuwahara, Nobuo Sakaguchi, Zusen Fan

Self-renewal and differentiation are the hallmarks of embryonic stem cells (ESCs). However, it is largely unknown about how the pluripotency is regulated. Here we demonstrate that Pcid2 is required for the maintenance of self-renewal both in mouse and human ESCs. Pcid2 plays a critical role in suppression of ESC differentiation. Pcid2 deficiency causes early embryonic lethality before the blastocyst stage. Pcid2 associates with EID1 and is present in the CBP/p300-EID1 complex in the ESCs. We show that MDM2 is an E3 ligase for K48-linked EID1 ubiquitination for its degradation. For the maintenance of self-renewal, Pcid2 binds to EID1 to impede the association with MDM2. Then EID1 is not degraded to sustain its stability to block the HAT activity of CBP/p300, leading to suppression of the developmental gene expression. Collectively, Pcid2 is present in the CBP/p300-EID1 complex to control the switch balance of mouse and human ESCs through modulation of EID1 degradation.

 

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