Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity
Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity
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DOI：
10.1242/dev.014340
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发表时间：
2008-04-15
期刊：
影响因子：
4.6
通讯作者：
Koseki, Haruhiko
中科院分区：
文献类型：
--
作者：
Endoh, Mitsuhiro;Endo, Takaho A.;Koseki, Haruhiko
多梳蛋白(Polycomb group，PcG)参与两个不同的多聚体蛋白复合体之一，即多梳抑制复合体1(PrC1)和多梳抑制复合体2(PrC2)，参与后生动物发育调节因子的可遗传沉默。虽然PRC2与包括Oct3/4在内的核心转录网络共享靶基因以维持胚胎干细胞，但目前仍不清楚PcG蛋白和核心转录网络是否在功能上相连。在这里，我们确定了核心的PRC1成分Ring1A/B在抑制小鼠ES细胞的发育调节中的重要作用，从而在维持ES细胞特性方面发挥了重要作用。很大一部分Prc1靶基因也被Oct3/4抑制。我们证明了Prc1与靶基因的结合是Oct3/4依赖的，而Oct3/4的结合不依赖于Prc1。此外，在GATA6表达诱导分化后，大多数Ring1A/B靶基因被去抑制，Ring1A/B与其靶基因的结合也减少。综上所述，这些结果表明，Ring1A/B介导的多梳沉默在核心转录调控电路下游发挥作用，以维持ES细胞的身份。
The Polycomb group (PcG) proteins mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes 1 (PRC1) and 2 (PRC2). Although PRC2 has been shown to share target genes with the core transcription network, including Oct3/4, to maintain embryonic stem (ES) cells, it is still unclear whether PcG proteins and the core transcription network are functionally linked. Here, we identify an essential role for the core PRC1 components Ring1A/B in repressing developmental regulators in mouse ES cells and, thereby, in maintaining ES cell identity. A significant proportion of the PRC1 target genes are also repressed by Oct3/4. We demonstrate that engagement of PRC1 at target genes is Oct3/4-dependent, whereas engagement of Oct3/4 is PRC1-independent. Moreover, upon differentiation induced by Gata6 expression, most of the Ring1A/B target genes are derepressed and the binding of Ring1A/B to their target loci is also decreased. Collectively, these results indicate that Ring1A/B-mediated Polycomb silencing functions downstream of the core transcriptional regulatory circuitry to maintain ES cell identity.