The Ash2l SDI Domain Is Required to Maintain the Stability and Binding of DPY30.
The Ash2l SDI Domain Is Required to Maintain the Stability and Binding of DPY30.
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DOI：
10.3390/cells11091450
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发表时间：
2022-04-25
期刊：
影响因子：
6
通讯作者：
Peng, Xiaozhong
中科院分区：
文献类型：
--
作者：
Ma, Mengjie;Zhou, Jiafeng;Ma, Zhihua;Chen, Hanxue;Li, Liang;Hou, Lin;Yin, Bin;Qiang, Boqin;Shu, Pengcheng;Peng, Xiaozhong
ASH 2L和DPY 30对于与SET 1（COMPASS）相关的复合物的组装和催化活性是重要的，该复合物催化组蛋白甲基化并调节基因表达。然而，COMPASS组件之间的规则并不完全清楚。在这里，我们利用小鼠模型和细胞系来观察Ash 2l消耗的结果，并发现DPY 30显著降低。分析ASH 2L ChIP-seq和RNA-seq数据排除了ASH 2L对DPY 30的转录和翻译调节。DPY 30的减少进一步归因于通过泛素介导的蛋白酶体途径的降解。我们还验证了ASH 2L Sdc 1 DPY 30相互作用（SDI）结构域中的三个氨基酸对于DPY 30的识别和结合是必需的。最后，我们意外地观察到DPY 30在Ash 2l耗尽的细胞中的过表达挽救了Ccnd 1的减少和异常的细胞周期，这表明DPY 30可以参与其他复合物来调节基因表达。总的来说，我们的研究结果首次揭示了DPY 30的存在依赖于与ASH 2L的结合，DPY 30通过泛素-蛋白酶体系统降解，并且他们进一步表明DPY 30的功能可以独立于ASH 2L。
ASH2L and DPY30 are important for the assembly and catalytic activity of the complex associated with SET1 (COMPASS), which catalyzes histone methylation and regulates gene expression. However, the regulations among COMPASS components are not fully understood. Here, we leveraged a mouse model and cell lines to observe the outcome of Ash2l depletion and found a significant decrease in DPY30. Analyzing ASH2L ChIP-seq and RNA-seq data excluded transcriptional and translational regulation of ASH2L to DPY30. The decrease in DPY30 was further attributed to the degradation via the ubiquitin-mediated proteasomal pathway. We also verified that three amino acids in the ASH2L Sdc1 DPY30 interaction (SDI) domain are essential for the recognition and binding of DPY30. Lastly, we unexpectedly observed that overexpression of DPY30 in Ash2l-depleted cells rescued the decrease in Ccnd1 and the abnormal cell cycle, which indicates that DPY30 can participate in other complexes to regulate gene expression. Overall, our results, for the first time, reveal that the existence of DPY30 relies on the binding with ASH2L, with degradation of DPY30 via the ubiquitin-proteasome system, and they further indicate that the function of DPY30 can be independent of ASH2L.
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影响因子：
8.8
作者：
Li, Liang;Ruan, Xiangbin;Peng, Xiaozhong
通讯作者：
Peng, Xiaozhong
影响因子：
8.8
作者：
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通讯作者：
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DOI：
10.1016/j.bbapap.2005.08.011
发表时间：
2005-12-01
影响因子：
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作者：
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影响因子：
21.3
作者：
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通讯作者：
Kouzarides, T