Chromatin signature of embryonic pluripotency is established during genome activation.
Chromatin signature of embryonic pluripotency is established during genome activation.
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受精后，胚胎基因组是无活性的，直到转录开始在母合子过渡。这种转变与多能细胞的形成相吻合，在哺乳动物中，多能细胞可用于产生胚胎干细胞。为了研究伴随多能性和基因组激活的染色质结构的变化，我们绘制了斑马鱼母系-合子转变前后组蛋白H3分子赖氨酸三甲基化修饰的基因组位置。三甲基化的赖氨酸27，这是抑制性的，和三甲基化的赖氨酸4，这是激活，没有检测到之前的过渡。基因组激活后，超过80%的基因被赖氨酸4三甲基化标记，包括许多失活的发育调控基因也被赖氨酸27三甲基化标记。连续染色质免疫沉淀表明，相同的启动子区域有两个三甲基化标记。这样的二价染色质结构域也存在于胚胎干细胞中，被认为是平衡基因的激活，同时保持它们的抑制。此外，我们发现许多失活的基因是唯一标记的赖氨酸4三甲基化。尽管这种激活修饰，这些单价基因既不表达，也不稳定结合RNA聚合酶II。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，赖氨酸4三甲基化标记可以在不存在序列特异性转录激活因子和RNA pol II稳定缔合的情况下形成，如诱导型转基因的分析所示。这些结果表明，二价和单价结构域可能平衡胚胎基因的激活，并与多能性的染色质配置文件是在母合子过渡建立。
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. Trimethylation of Lysine 27, which is repressive, and trimethylation of Lysine 4, which is activating, were not detected before the transition. After genome activation, more than 80% of genes were marked by Lysine 4 trimethylation, including many inactive developmental regulatory genes that were also marked by Lysine 27 trimethylation. 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. In addition, we found many inactive genes that were uniquely marked by Lysine 4 trimethylation. Despite this activating modification, these monovalent genes were neither expressed nor stably bound by RNA polymerase II. Inspection of published datasets revealed similar monovalent domains in embryonic stem cells. Moreover, Lysine 4 trimethylation marks could form in the absence of both sequence-specific transcriptional activators and stable association of RNA pol II, as indicated by the analysis of an inducible transgene. These results suggest 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.
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