Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Nature. 2010 Apr 8;464(7290):922-6. doi: 10.1038/nature08866. Epub 2010 Mar 24.
After fertilization the embryonic genome is inactive until transcription is initiated during the maternal-zygotic transition. This transition coincides with the formation of pluripotent cells, which in mammals can be used to generate embryonic stem cells. To study the changes in chromatin structure that accompany pluripotency and genome activation, we mapped the genomic locations of histone H3 molecules bearing lysine trimethylation modifications before and after the maternal-zygotic transition in zebrafish. Histone H3 lysine 27 trimethylation (H3K27me3), which is repressive, and H3K4me3, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by H3K4me3, including many inactive developmental regulatory genes that were also marked by H3K27me3. Sequential chromatin immunoprecipitation demonstrated that the same promoter regions had both trimethylation marks. Such bivalent chromatin domains also exist in embryonic stem cells and are thought to poise genes for activation while keeping them repressed. Furthermore, we found many inactive genes that were uniquely marked by H3K4me3. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published data sets revealed similar monovalent domains in embryonic stem cells. Moreover, H3K4me3 marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA polymerase II, as indicated by the analysis of an inducible transgene. These results indicate that bivalent and monovalent domains might poise embryonic genes for activation and that the chromatin profile associated with pluripotency is established during the maternal-zygotic transition.
受精后，胚胎基因组在母源-合子过渡期间转录起始之前处于非活性状态。 这种转变与多能细胞的形成相吻合，在哺乳动物中，多能细胞可用于生成胚胎干细胞。为了研究伴随多能性和基因组激活而发生的染色质结构变化，我们在斑马鱼中绘制了母源-合子过渡前后组蛋白 H3 分子上赖氨酸三甲基化修饰的基因组位置。 在过渡之前，未检测到组蛋白 H3 赖氨酸 27 三甲基化（H3K27me3）和激活的 H3K4me3。 基因组激活后，超过 80％的基因被 H3K4me3 标记，包括许多被 H3K27me3 标记的失活发育调控基因。 顺序染色质免疫沉淀表明，相同的启动子区域具有两种三甲基化标记。 这种双价染色质域也存在于胚胎干细胞中，被认为使基因处于激活状态，同时保持其抑制状态。 此外，我们发现许多失活基因仅被 H3K4me3 标记。 尽管有这种激活修饰，但这些单价基因既未表达也未被 RNA 聚合酶 II 稳定结合。 对已发表的数据集的检查揭示了胚胎干细胞中类似的单价结构域。 此外，正如诱导型转基因分析所表明的那样，在没有序列特异性转录激活因子和 RNA 聚合酶 II 稳定结合的情况下，也可以形成 H3K4me3 标记。 这些结果表明，双价和单价结构域可能使胚胎基因处于激活状态，并且与多能性相关的染色质图谱是在母源-合子过渡期间建立的。
