Abstract：
Repeat element transcription plays a vital role in early embryonic development. The expression of repeats such as MERVL characterises mouse embryos at the 2-cell stage and defines a 2-cell-like cell (2CLC) population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify the forkhead domain transcription factor FOXD3 as a regulator of major satellite repeats and MERVL transcription in mouse embryonic stem cells. FOXD3 binds to and recruits the histone methyltransferase SUV39H1 to MERVL and major satellite repeats, consequentially repressing the transcription of these repeats by the establishment of the H3K9me3 heterochromatin modification. Notably, depletion of FOXD3 leads to the de-repression of MERVL and major satellite repeats as well as a subset of genes expressed in the 2-cell state, shifting the balance between the stem cell and 2-cell-like population in culture. Thus, FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.
摘要：
重复元件转录在早期胚胎发育中起着至关重要的作用。重复序列如MERVL的表达在2细胞阶段表征小鼠胚胎,并在小鼠胚胎干细胞培养物中定义2细胞样细胞(2CLC)群体。重复元件序列含有许多转录因子的结合位点。我们确定叉头结构域转录因子FOXD3是小鼠胚胎干细胞中主要卫星重复和MERVL转录的调节因子。FOXD3结合并招募组蛋白甲基转移酶SUV39H1至MERVL和主要卫星重复序列，通过建立H3K9me3异染色质修饰，从而抑制这些重复序列的转录。值得注意的是,FOXD3的消耗导致MERVL和主要的卫星重复序列以及在2细胞状态中表达的基因子集的去抑制。在培养中改变干细胞和2细胞样群体之间的平衡。因此，FOXD3作为重复转录的负调节因子，赋予这个转录因子一个新的功能。
