PDF(Pubmed)
Abstract：
Upon mammalian fertilization, zygotic genome activation (ZGA) and activation of transposable elements (TEs) occur in early embryos to establish totipotency and support embryogenesis. However, the molecular mechanisms controlling the expression of these genes in mammals remain poorly understood. The 2-cell-like population of mouse embryonic stem cells (mESCs) mimics cleavage-stage embryos with transient Dux activation. In this study, we demonstrated that deficiency of the transcription factor OTX2 stimulates the expression of ZGA genes in mESCs. Further analysis revealed that OTX2 is incorporated at the Dux locus with corepressors for transcriptional inhibition. We also found that OTX2 associates with TEs and silences the subtypes of TEs. Therefore, OTX2 protein plays an important role in ZGA and TE expression in mESCs to orchestrate the transcriptional network.
摘要：
哺乳动物受精后，合子基因组激活（ZGA）和转座因子（TE）的激活发生在早期胚胎中，以建立全能性并支持胚胎发生。然而,控制这些基因在哺乳动物中表达的分子机制仍然知之甚少。小鼠胚胎干细胞（mESC）的2细胞样群体模拟具有瞬时Dux激活的卵裂期胚胎。在这项研究中,我们证明转录因子OTX2的缺乏刺激mESC中ZGA基因的表达。进一步的分析显示OTX2在Dux基因座处与用于转录抑制的辅抑制因子结合。我们还发现OTX2与TE相关，并沉默TE的亚型。因此,OTX2蛋白在mESCs的ZGA和TE表达中发挥重要作用，以协调转录网络。
