DPPA2 and DPPA4 are necessary to establish a 2C-like state in mouse embryonic stem cells
DPPA2 and DPPA4 are necessary to establish a 2C-like state in mouse embryonic stem cells
复制标题
DOI：
10.15252/embr.201847382
复制
发表时间：
2019-05-01
期刊：
影响因子：
7.7
通讯作者：
Trono, Didier
中科院分区：
文献类型：
--
作者：
De Iaco, Alberto;Coudray, Alexandre;Trono, Didier
转录沉默的卵母细胞受精后，通过合子基因组激活（ZGA）启动来自两条亲本染色体的表达，发生在小鼠2细胞（2C）阶段。首先被转录的元素是Dux基因，其产物诱导广泛的ZGA基因，以及一个进化的最近LINE-1逆转录转座子的子集，其调节早期胚胎中的染色质可及性。到目前为止，激活Dux和LINE-1转录的母系遗传因子仍然未知。小鼠胚胎干细胞（mESC）在培养中重现了ZGA的某些方面，这是由于当Dux、其靶基因和LINE-1整合体表达时，它们能够循环通过2C样阶段。在这里，我们确定了paradox蛋白DPPA 2和DPPA 4作为必要的Dux和LINE-1在mESC中的表达的激活。由于它们的编码RNA通过母体传递到受精卵，因此这些因子可能是鼠ZGA的重要上游介质。
After fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through zygotic genome activation (ZGA), occurring in the mouse at the 2-cell (2C) stage. Among the first elements to be transcribed are the Dux gene, the product of which induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons that regulate chromatin accessibility in the early embryo. The maternally inherited factors that activate Dux and LINE-1 transcription have so far remained unknown. Mouse embryonic stem cells (mESCs) recapitulate some aspects of ZGA in culture, owing to their ability to cycle through a 2C-like stage when Dux, its target genes, and LINE-1 integrants are expressed. Here, we identify the paralog proteins DPPA2 and DPPA4 as necessary for the activation of Dux and LINE-1 expression in mESCs. Since their encoding RNAs are maternally transmitted to the zygote, it is likely that these factors are important upstream mediators of murine ZGA.