Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10783-90. doi: 10.1073/pnas.0914507107. Epub 2010 May 17.
A unique property of the mammalian embryo is that stem cells can be derived from its early tissue lineages. These lineages will give rise to the fetus as well as essential extraembryonic tissues. Understanding how chromatin regulation participates in establishment of these lineages in the embryo and their derived stem cells provides insight that will critically inform our understanding of embryogenesis and stem cell biology. Here, we compare the genomewide location of active and repressive histone modifications in embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm stem cells from the mouse. Our results show that the active modification H3K4me3 has a similar role in the three stem cell types, but the repressive modification H3K27me3 varies in abundance and genomewide distribution. Thus, alternative mechanisms mediate transcriptional repression in stem cells from the embryo. In addition, using carrier chromatin immunoprecipitation we show that bivalent histone domains seen in embryonic stem cells exist in pluripotent cells of the early embryo. However, the epigenetic status of extraembryonic progenitor cells in the embryo did not entirely reflect the extraembryonic stem cell lines. These studies indicate that histone modification mechanisms may differ between early embryo lineages and emphasize the importance of examining in vivo and in vitro progenitor cells.
哺乳动物胚胎的一个独特性质是,干细胞可以从其早期组织谱系中衍生而来。这些谱系将产生胎儿以及必不可少的胚胎外组织。了解染色质调节如何参与胚胎中这些谱系的建立及其衍生的干细胞,为我们理解胚胎发生和干细胞生物学提供了重要的信息。在这里,我们比较了来自小鼠的胚胎干细胞、滋养层干细胞和胚胎外内胚层干细胞中活性和抑制性组蛋白修饰的全基因组定位。我们的结果表明,活性修饰 H3K4me3 在这三种干细胞类型中具有相似的作用,但抑制性修饰 H3K27me3 的丰度和全基因组分布不同。因此,在胚胎干细胞中,转录抑制由替代机制介导。此外,我们使用载体染色质免疫沉淀实验表明,在胚胎干细胞中看到的双价组蛋白结构域存在于早期胚胎的多能细胞中。然而,胚胎中胚胎外祖细胞的表观遗传状态并没有完全反映胚胎外干细胞系。这些研究表明,组蛋白修饰机制可能在早期胚胎谱系之间存在差异,并强调了检查体内和体外祖细胞的重要性。