The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation.
The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation.
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DOI：
10.1038/ncb1351
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发表时间：
2006-02
影响因子：
21.3
通讯作者：
Magnuson, T
中科院分区：
文献类型：
--
作者：
Kalantry, S;Mills, KC;Yee, D;Otte, AP;Panning, B;Magnuson, T
Polycomb组（PcG）编码一组进化上保守的染色质修饰蛋白，其被认为通过稳定沉默基因表达来维持细胞转录记忆。在PcG蛋白Eed突变的小鼠胚胎中，X染色体失活（XCI）在胚胎外组织中不能稳定维持。Eed是组蛋白-甲基转移酶复合物的一种成分，由于其富集在早期小鼠胚胎细胞和胚胎外滋养外胚层谱系干细胞中的无活性X染色体（Xi）上，因此被认为有助于未分化细胞中的稳定沉默。在这里，我们证明了Xi在Eed−/−滋养层干细胞（TS）和Eed−/−胚胎滋养外胚层衍生的胚外外胚层细胞中保持转录沉默，尽管缺乏通常表征Xi兼性异染色质的PcG介导的组蛋白修饰。虽然未分化的Eed−/− TS细胞保持XCI，但当这些细胞分化时，Xi发生重新激活。这些结果表明，PcG复合物不是维持未分化干细胞中Xi转录沉默所必需的。相反，PcG蛋白似乎通过阻止分化过程中兼性异染色质的转录激活来传播细胞记忆。
The Polycomb group (PcG) encodes an evolutionarily conserved set of chromatin-modifying proteins that are thought to maintain cellular transcriptional memory by stably silencing gene expression. In mouse embryos mutated for the PcG protein Eed, X-chromosome inactivation (XCI) is not stably maintained in extra-embryonic tissues. Eed is a component of a histone-methyltransferase complex that is thought to contribute to stable silencing in undifferentiated cells due to its enrichment on the inactive X-chromosome (Xi) in cells of the early mouse embryo and in stem cells of the extra-embryonic trophectoderm lineage. Here we demonstrate that the Xi in Eed−/− trophoblast stem (TS) cells and in cells of the trophectoderm-derived extra-embryonic ectoderm in Eed−/− embryos remains transcriptionally silent, despite lacking the PcG-mediated histone modifications that normally characterize the facultative heterochromatin of the Xi. While undifferentiated Eed−/− TS cells maintained XCI, reactivation of the Xi occurred when these cells were differentiated. These results indicate that PcG complexes are not necessary to maintain transcriptional silencing of the Xi in undifferentiated stem cells. Instead, PcG proteins appear to propagate cellular memory by preventing transcriptional activation of facultative heterochromatin during differentiation.
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通讯作者：
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