SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development.
SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development.
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DOI：
10.1016/j.molcel.2010.03.005
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发表时间：
2010-04-23
期刊：
影响因子：
16
通讯作者：
Yeh ET
中科院分区：
文献类型：
--
作者：
Kang X;Qi Y;Zuo Y;Wang Q;Zou Y;Schwartz RJ;Cheng J;Yeh ET
SUMO特异性蛋白酶2（SENP 2）在体外具有广泛的去SUMO化活性。然而，SENP 2的生物学功能在很大程度上是未知的。在这里，我们发现小鼠SENP 2基因的缺失导致胚胎心脏缺陷，并降低了心脏发育所必需的Gata 4和Gata 6的表达。SENP 2主要通过改变其启动子上多梳抑制复合物1（PRC 1）亚基Pc 2/CBX 4的占有率来调节Gata 4和Gata 6的转录。我们证明了Pc 2/CBX 4是SENP 2在体内的靶点，并且SUMO化对于Pc 2/CBX 4介导的PRC 1募集到甲基化组蛋白3的K27（H3 K27 me 3）是必需的。在SENP 2基因缺失的胚胎中，SUMO化的Pc 2/CBX 4积累，并且PcG靶基因启动子上的Pc 2/CBX 4占据显著增加，导致Gata 4和Gata 6转录的抑制。我们的研究结果揭示了去SUMO化通过一种新的机制在PcG靶基因表达调控中的关键作用。
SUMO-specific protease 2 (SENP2) has a broad de-SUMOylation activity in vitro. However, the biological function of SENP2 is largely unknown. Here, we show that deletion of SENP2 gene in mouse causes defects in the embryonic heart and reduces the expression of Gata4 and Gata6, which are essential for cardiac development. SENP2 regulates transcription of Gata4 and Gata6 mainly through alteration of occupancy of Pc2/CBX4, a Polycomb Repressive Complex 1 (PRC1) subunit, on its promoters. We demonstrate that Pc2/CBX4 is a target of SENP2 in vivo and that SUMOylation is essential for Pc2/CBX4-mediated PRC1 recruitment to methylated histone 3 at K27 (H3K27me3). In SENP2 null embryo, SUMOylated Pc2/CBX4 accumulates and Pc2/CBX4 occupancy on the promoters of PcG target genes is markedly increased, leading to repression of Gata4 and Gata6 transcription. Our results reveal a critical role for de-SUMOylation in the regulation of PcG target gene expression through a novel mechanism.
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