Stem cells primed for action - Polycomb repressive complexes restrain the expression of lineage-specific regulators in embryonic stem cells
Stem cells primed for action - Polycomb repressive complexes restrain the expression of lineage-specific regulators in embryonic stem cells
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DOI：
10.4161/cc.5.13.2927
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发表时间：
2006-07-01
期刊：
影响因子：
4.3
通讯作者：
Fisher, Amanda G.
中科院分区：
文献类型：
--
作者：
Jorgensen, Helle F.;Giadrossi, Sara;Fisher, Amanda G.
干细胞的特点是具有自我更新和产生能够沿着几个确定的谱系路径分化的后代的能力。胚胎干（ES）细胞源自早期胚胎的内细胞团（ICM），可以为发育中胚胎的所有组织做出贡献。探索 ES 细胞多能性和谱系诱导是如何实现的，对于理解正常发育和成功应用基于干细胞的疗法非常重要。最近的一系列研究表明，ES 细胞的染色质谱是不寻常的，并揭示了多梳抑制复合物 (PRC) 在维持多能性方面的关键作用。在人和小鼠 ES 细胞中，许多编码谱系规范所需转录因子的基因结合 PRC2 并携带二价（或相反）组蛋白特征，富含活性染色质的常规指标，例如乙酰化 H3K9 和甲基化 H3K4，同时位于抑制性三甲基化 H3K27 的结构域内。缺乏 H3K27 甲基化的突变 ES 细胞不恰当地表达这些基因，表明 PRC2 抑制 ES 细胞中谱系特异性基因程序。在这里，我们讨论这些新发现的意义，并探讨 PRC1 和 PRC2 在调节 ES 细胞中谱系特异性基因表达方面的相互依赖性。
Stem cells are characterised by a capacity to self renew and generate progeny capable of differentiating along several defined lineage paths. Embryonic Stem (ES) cells are derived from the inner cell mass (ICM) of early-stage embryos and can contribute to all tissues of the developing embryo. Discovering how ES cell pluripotency and lineage induction is achieved is important for understanding normal development and for successfully applying stem cell-based therapies. A series of recent studies have shown that the chromatin profile of ES cells is unusual and have revealed a critical role for the Polycomb Repressive Complexes (PRCs) in maintaining pluripotency. In human and mouse ES cells many genes that encode transcription factors that are required for lineage specification bind PRC2 and carry bivalent ( or opposing) histone signatures, being enriched for conventional indicators of active chromatin such as acetylated H3K9 and methylated H3K4, while lying within domains of repressive trimethylated H3K27. Mutant ES cells that lack H3K27 methylation inappropriately expressed these genes showing that PRC2 represses lineage-specific gene programs in ES cells. Here we discuss the implications of these new discoveries and explore the interdependence of PRC1 and PRC2 in regulating lineage-specific gene expression in ES cells.