Department of Stem Cell Biology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University., 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.
Advanced Science Research Center, Kanazawa University. 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.
Sci Rep. 2017 Oct 25;7(1):14059. doi: 10.1038/s41598-017-14362-4.
The human Baf (Brg1/Brm associated factor) complex, also known as the mammalian SWI/SNF chromatin-remodeling complex, is involved in a variety of cellular processes. The pluripotency and self-renewal abilities are major characteristics of embryonic stem (ES) cells and are regulated by the ES cell-specific BAF (esBAF) complex. Baf53a is one of the subunits of the esBAF complex. Here, we found that Baf53a was expressed in undifferentiated ES cells and that it interacted with Oct3/4. Analyses of tetracycline-inducible Baf53a conditional knockout ES cells revealed that the undifferentiated markers, including Nanog and Oct3/4, were expressed in Baf53a-deficient ES cells; however, growth of the cells was repressed, and expression of p53, p21, and cleaved Caspase 3 was increased. Cell death of Baf53a-deficient ES cells was rescued by overexpression of Baf53a, but not by the Baf53a M3 mutant (E388A/R389A/R390A). Interestingly, Baf53b, a homologue of Baf53a, rescued cell death of Baf53a-deficient ES cells. Baf53a-deficient ES cells overexpressing exogenous Baf53a or Baf53b remained in the undifferentiated state, proliferated, and repressed expression of p21. In summary, our findings suggest that Baf53a is involved in the survival of ES cells by regulating p53 and Caspase3, and that Baf53b is able to compensate for this functional aspect of Baf53a.
人类 Baf（Brg1/Brm 相关因子）复合物，也称为哺乳动物 SWI/SNF 染色质重塑复合物，参与多种细胞过程。多能性和自我更新能力是胚胎干细胞（ES 细胞）的主要特征，受 ES 细胞特异性 BAF（esBAF）复合物的调节。Baf53a 是 esBAF 复合物的一个亚基。在这里，我们发现 Baf53a 在未分化的 ES 细胞中表达，并与 Oct3/4 相互作用。对四环素诱导的 Baf53a 条件性敲除 ES 细胞的分析表明，未分化的标记物，包括 Nanog 和 Oct3/4，在 Baf53a 缺陷型 ES 细胞中表达；然而，细胞生长受到抑制，p53、p21 和裂解 Caspase 3 的表达增加。Baf53a 缺陷型 ES 细胞的细胞死亡通过 Baf53a 的过表达得到挽救，但不是通过 Baf53a M3 突变体（E388A/R389A/R390A）。有趣的是，Baf53a 的同源物 Baf53b 挽救了 Baf53a 缺陷型 ES 细胞的细胞死亡。过表达外源 Baf53a 或 Baf53b 的 Baf53a 缺陷型 ES 细胞仍保持未分化状态，增殖，并抑制 p21 的表达。总之，我们的研究结果表明，Baf53a 通过调节 p53 和 Caspase3 参与 ES 细胞的存活，并且 Baf53b 能够补偿 Baf53a 的这一功能方面。
