Wang Feng, Shin JongDae, Shea Jeremy M, Yu Jun, Bošković Ana, Byron Meg, Zhu Xiaochun, Shalek Alex K, Regev Aviv, Lawrence Jeanne B, Torres Eduardo M, Zhu Lihua J, Rando Oliver J, Bach Ingolf
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States.
Department of Cell Biology, College of Medicine, Konyang University, Daejeon, Korea.
Elife. 2016 Sep 19;5:e19127. doi: 10.7554/eLife.19127.
Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both (also known as Rnf12) and the long non-coding RNA . Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of on the temporal regulation of iXCI and . Our results reveal crucial roles of for the maintenance of high RNA levels, clouds and X-silencing in female embryos at blastocyst stages, while initial expression appears -independent. We find further that X/A upregulation is initiated in early male and female preimplantation embryos.
哺乳动物的X连锁基因表达受到高度调控，因为雌性细胞含有两条X染色体，而雄性细胞只含有一条X染色体。为了调整两性之间的X基因剂量，雌性小鼠植入前胚胎会经历一种印记形式的X染色体失活（iXCI），这需要Rnf12（也称为Rnf12）和长链非编码RNA Xist。此外，人们认为来自单一活性X的基因表达会上调，以纠正双等位基因常染色体（A）基因的表达。我们将小鼠遗传学与单个小鼠胚胎的RNA测序相结合，以研究Rnf12在iXCI和Xist的时间调控中的作用。我们的结果揭示了Rnf12在维持囊胚期雌性胚胎中高Xist RNA水平、Xist云形成和X染色体沉默方面的关键作用，而最初的Rnf12表达似乎与Xist无关。我们进一步发现，X/A上调在早期雄性和雌性植入前胚胎中就已启动。
