The polycomb group protein Suz12 is required for embryonic stem cell differentiation
The polycomb group protein Suz12 is required for embryonic stem cell differentiation
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DOI：
10.1128/mcb.01432-06
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发表时间：
2007-05-01
影响因子：
5.3
通讯作者：
Helin, Kristian
中科院分区：
文献类型：
--
作者：
Pasini, Diego;Bracken, Adrian P.;Helin, Kristian
Polycomb group（PcG）蛋白形成多蛋白复合物，称为Polycomb抑制复合物（PRCs）。PRC 2包含PcG蛋白EZH 2、SUZ 12和EED，并通过组蛋白H3的赖氨酸（K）27的甲基化抑制转录（113）。Suz 12是PRC 2活性所必需的，其失活导致小鼠胚胎的早期致死。在这里，我们证明，Suz 12（-/-）小鼠胚胎干细胞（ES）细胞可以建立和扩大在组织培养。Suz 12（-/-）ES细胞的特征在于H3 K27三甲基化（H3 K27 me 3）的整体丧失和分化特异性基因的较高表达水平。此外，Suz 12（-/-）ES细胞在适当分化中受损，导致ES细胞标记物的抑制以及分化特异性基因的活化缺乏。最后，我们证明了在ES细胞分化过程中，PcGs被积极招募到几个基因中，尽管H3 K27 me 3水平增加，但并不总是足以阻止转录激活。总之，我们证明了Suz 12是建立ES细胞分化所需的特异性表达程序所必需的。此外，我们提供的证据表明，PcGs有不同的机制来调节细胞分化过程中的转录。
Polycomb group (PcG) proteins form multiprotein complexes, called Polycomb repressive complexes (PRCs). PRC2 contains the PcG proteins EZH2, SUZ12, and EED and represses transcription through methylation of lysine (K) 27 of histone H3 (113). Suz12 is essential for PRC2 activity and its inactivation results in early lethality of mouse embryos. Here, we demonstrate that Suz12(-/-) mouse embryonic stem (ES) cells can be established and expanded in tissue culture. The Suz12(-/-) ES cells are characterized by global loss of H3K27 trimethylation (H3K27me3) and higher expression levels of differentiation-specific genes. Moreover, Suz12(-/-) ES cells are impaired in proper differentiation, resulting in a lack of repression of ES cell markers as well as activation of differentiation-specific genes. Finally, we demonstrate that the PcGs are actively recruited to several genes during ES cell differentiation, which despite an increase in H3K27me3 levels is not always sufficient to prevent transcriptional activation. In summary, we demonstrate that Suz12 is required for the establishment of specific expression programs required for ES cell differentiation. Furthermore, we provide evidence that PcGs have different mechanisms to regulate transcription during cellular differentiation.