SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States
SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States
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DOI：
10.1016/j.stem.2018.10.001
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发表时间：
2018-11-01
期刊：
影响因子：
23.9
通讯作者：
Dejean, Anne
中科院分区：
文献类型：
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作者：
Cossec, Jack-Christophe;Theurillat, Ilan;Dejean, Anne
了解保护细胞身份的一般原则应该揭示对不同细胞类型规范的共同机制的重要见解。在这里，我们证明 SUMO 修饰可以在多种情况下稳定细胞命运。低糖酰化增强体外和体内的多能性重编程，增加谱系转分化，并促进白血病细胞分化。抑制胚胎干细胞 (ESC) 中的 sumoylation 可促进其转化为 2 细胞胚胎样 (2C 样) 细胞。在重编程为多能性的过程中，SUMO 在成纤维细胞增强子上发挥作用，保留体细胞转录因子以及 Oct4、Sox2 和 Klf4，从而阻止体细胞增强子失活。相比之下，在 ESC 中，SUMO 在异染色质上发挥作用，沉默 2C 程序，在全基因组范围内维持适当的 H3K9me3 水平，并通过触发 sumoylated PRC1.6 和 Kap/Setdb1 抑制复合物的募集来抑制 Dux 位点。总之，这些研究表明 SUMO 作为粘合剂作用于染色质，以稳定体细胞和多能状态的关键决定因素。
Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vitro and in vivo, increases lineage transdifferentiation, and facilitates leukemic cell differentiation. Suppressing sumoylation in embryonic stem cells (ESCs) promotes their conversion into 2-cell-embryo-like (2C-like) cells. During reprogramming to pluripotency, SUMO functions on fibroblastic enhancers to retain somatic transcription factors together with Oct4, Sox2, and Klf4, thus impeding somatic enhancer inactivation. In contrast, in ESCs, SUMO functions on heterochromatin to silence the 2C program, maintaining both proper H3K9me3 levels genome-wide and repression of the Dux locus by triggering recruitment of the sumoylated PRC1.6 and Kap/Setdb1 repressive complexes. Together, these studies show that SUMO acts on chromatin as a glue to stabilize key determinants of somatic and pluripotent states.