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Extensive SUMO Modification of Repressive Chromatin Factors Distinguishes Pluripotent from Somatic Cells.
Cell Reports ( IF 7.5 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.celrep.2020.108146
Ilan Theurillat 1 , Ivo A Hendriks 2 , Jack-Christophe Cossec 3 , Alexandra Andrieux 3 , Michael L Nielsen 2 , Anne Dejean 3
Affiliation  

Post-translational modification by SUMO is a key regulator of cell identity. In mouse embryonic fibroblasts (MEFs), SUMO impedes reprogramming to pluripotency, while in embryonic stem cells (ESCs), it represses the emergence of totipotent-like cells, suggesting that SUMO targets distinct substrates to preserve somatic and pluripotent states. Using MS-based proteomics, we show that the composition of endogenous SUMOylomes differs dramatically between MEFs and ESCs. In MEFs, SUMO2/3 targets proteins associated with canonical SUMO functions, such as splicing, and transcriptional regulators driving somatic enhancer selection. In contrast, in ESCs, SUMO2/3 primarily modifies highly interconnected repressive chromatin complexes, thereby preventing chromatin opening and transitioning to totipotent-like states. We also characterize several SUMO-modified pluripotency factors and show that SUMOylation of Dppa2 and Dppa4 impedes the conversion to 2-cell-embryo-like states. Altogether, we propose that rewiring the repertoire of SUMO target networks is a major driver of cell fate decision during embryonic development.



中文翻译:

抑制性染色质因子的广泛SUMO修饰可区分体细胞的多能性。

SUMO的翻译后修饰是细胞身份的关键调节因子。在小鼠胚胎成纤维细胞(MEF)中,SUMO阻止重编程为多能性,而在胚胎干细胞(ESC)中,它抑制全能样细胞的出现,表明SUMO靶向不同的底物以保持体细胞和多能性状态。使用基于MS的蛋白质组学,我们证明MEF和ESC之间内源SUMOylomes的组成差异很大。在MEF中,SUMO2 / 3靶向与规范SUMO功能相关的蛋白质,例如剪接和驱动体细胞增强子选择的转录调节子。相反,在ESC中,SUMO2 / 3主要修饰高度互连的阻抑性染色质复合物,从而防止了染色质开放并转变为全能状。我们还表征了几个SUMO修饰的多能性因子,并表明Dppa2和Dppa4的SUMOylation阻碍了向2细胞胚样状态的转化。总而言之,我们建议重新连接SUMO目标网络的组成部分是胚胎发育过程中细胞命运决定的主要驱动力。

更新日期:2020-09-15
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