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首页> 外文期刊>Epigenetics & Chromatin >ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the trophectoderm lineage
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ERG-associated protein with SET domain (ESET)-Oct4 interaction regulates pluripotency and represses the trophectoderm lineage

机译：与SET域（ESET）-Oct4相互作用的ERG相关蛋白调节多能性并抑制滋养外胚层谱系

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Background Pluripotency, the capacity for indefinite self-renewal and differentiation into diverse cell types is a unique state exhibited by embryonic stem (ES) cells. Transcriptional regulators, such as Oct4, are critical for pluripotency, but the role of epigenetic modifiers remains to be fully elucidated. Results Here, we show that ERG-associated protein with SET domain (ESET), a histone methyltransferase enzyme, maintains pluripotency through repression of Cdx2, a key trophectoderm determinant, by histone H3 lysine 9 trimethylation (H3K9me3) of the promoter region. Notably, this repression is mediated through the synergistic function of small ubiquitin-related modifier (SUMO)ylated ESET and Oct4. ESET localises to the promyelocytic leukaemia (PML) nuclear bodies and is SUMOylated in ES cells. Interaction of ESET with Oct4 depends on a SUMO-interacting motif (SIM) in Oct4, which is critical for the repression of Cdx2. Conclusion Loss of ESET or Oct4 results in strikingly similar phenotypes both in ES cells with their differentiation into trophectoderm cells, and in early embryos where there is a failure of development of the pluripotent inner cell mass (ICM) of blastocysts. We propose that SUMOylated ESET-Oct4 complex is critical for both the initiation and maintenance of pluripotency through repression of differentiation, particularly of the trophectoderm lineage by epigenetic silencing of Cdx2.
机译：背景多能性，无限自我更新和分化为多种细胞类型的能力是胚胎干（ES）细胞展现的独特状态。转录调节因子（例如Oct4）对于多能性至关重要，但是表观遗传修饰因子的作用尚待充分阐明。结果在这里，我们显示带有SET域（ESET）的ERG相关蛋白（组蛋白甲基转移酶）通过启动子区的组蛋白H3赖氨酸9三甲基化（H3K9me3）抑制Cdx2（关键的滋养外胚层决定簇）来维持多能性。值得注意的是，这种抑制作用是通过小泛素相关修饰剂（SUMO）酰化的ESET和Oct4的协同功能介导的。 ESET定位于早幼粒细胞白血病（PML）核体，并在ES细胞中被SUMO化。 ESET与Oct4的相互作用取决于Oct4中的SUMO相互作用基序（SIM），这对于抑制Cdx2至关重要。结论ESET或Oct4的缺失在ES细胞分化为滋养外胚层细胞以及早期胚胎中均表现出惊人相似的表型，胚泡的发育多能内部细胞团（ICM）发育失败。我们提出，SUMOylated ESET-Oct4复合物对于通过抑制分化，尤其是通过Cdx2的表观遗传沉默对滋养外胚层谱系的多能性的启动和维持至关重要。

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