The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming
The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming
复制标题
Zscan4-Tet2 转录连接调节代谢重连并增强蛋白质稳态以促进重编程
DOI：
10.1016/j.celrep.2020.107877
复制
发表时间：
2020-07-14
期刊：
影响因子：
8.8
通讯作者：
Ye, Dan
中科院分区：
文献类型：
--
作者：
Cheng, Zhou-Li;Zhang, Meng-Li;Ye, Dan
进化上保守的SCAN（以SRE-ZBP、CTfin 51、AW-1和Number 18 cDNA命名）-含有锌指结构域的转录因子（ZFCAN）已经在小鼠和人类基因组中被发现。Zscan 4在植入前胚胎的合子基因组激活（ZGA）和诱导多能干细胞（iPSC）重编程期间瞬时表达。然而，很少有人知道Zscan 4的机制，这些过程的细胞命运控制。在这里，我们表明，Zscan 4f，一个代表性的蛋白质，是能够招募Tet 2通过其扫描结构域。Zscan 4f-Tet 2相互作用促进DNA去甲基化并调节靶基因的表达，特别是那些编码糖酵解酶和蛋白酶体亚基的基因。Zscan 4f调节代谢重新布线，增强蛋白酶体功能，并最终促进1 PSC生成。这些结果鉴定了Zscan 4f作为Tet 2在调节靶基因和促进iPSC产生中的重要伙伴，并表明SCAN家族转录因子共有的可能和共同的机制来募集10 - 11易位（泰特）DNA双加氧酶以调节不同的细胞过程，包括重编程。
Evolutionarily conserved SCAN (named after SRE-ZBP, CTfin51, AW-1, and Number 18 cDNA)-domain-containing zinc finger transcription factors (ZSCAN) have been found in both mouse and human genomes. Zscan4 is transiently expressed during zygotic genome activation (ZGA) in preimplantation embryos and induced pluripotent stem cell (iPSC) reprogramming. However, little is known about the mechanism of Zscan4 underlying these processes of cell fate control. Here, we show that Zscan4f, a representative of ZSCAN proteins, is able to recruit Tet2 through its SCAN domain. The Zscan4f-Tet2 interaction promotes DNA demethylation and regulates the expression of target genes, particularly those encoding glycolytic enzymes and proteasome subunits. Zscan4f regulates metabolic rewiring, enhances proteasome function, and ultimately promotes 1PSC generation. These results identify Zscan4f as an important partner of Tet2 in regulating target genes and promoting iPSC generation and suggest a possible and common mechanism shared by SCAN family transcription factors to recruit ten-eleven translocation (TET) DNA dioxygenases to regulate diverse cellular processes, including reprogramming.