DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates

doi:10.1016/j.isci.2022.104948

	DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates
	Zhao, Lijie 1,2; Huang, Naizhe 1,2; Mencius, Jun 3; Li, Yanjing 3; Xu, Ying 1; Zheng, Yongxin 3; He, Wei ; Li, Na 4; Zheng, Jun ; Zhuang, Min5 ; Quan, Shu 3,6; Chen, Yong1,2,5
	2022-09-16
发表期刊	ISCIENCE (IF:4.6[JCR-2023],5.0[5-Year])
EISSN	2589-0042
卷号	25 期号:9
发表状态	已发表
DOI	10.1016/j.isci.2022.104948
摘要	Dumpy-30 (DPY30) is a conserved component of the mixed lineage leukemia (MLL) family complex and is essential for robust methyltransferase activity of MLL complexes. However, the biochemical role of DPY30 in stimulating methyl-transferase activity of MLL complexes remains elusive. Here, we demonstrate that DPY30 plays a crucial role in regulating MLL1 activity through two com-plementary mechanisms: A nucleosome-independent mechanism and a nucleo-some-specific mechanism. DPY30 functions as an ASH2L-specific stabilizer to increase the stability of ASH2L and enhance ASH2L-mediated interactions. As a result, DPY30 promotes the compaction and stabilization of the MLL1 complex, consequently increasing the HKMT activity of the MLL1 complex on diverse sub-strates. DPY30-stabilized ASH2L further acquires additional interfaces with H3 and nucleosomal DNA, thereby boosting the methyltransferase activity of the MLL1 complex on nucleosomes. These results collectively highlight the crucial and conserved roles of DPY30 in the complex assembly and activity regulation of MLL family complexes.
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收录类别	SCI ; SCIE
语种	英语
资助项目	Shanghai Pilot Program for Basic Research from Chinese Academy of Science, Shanghai Branch[XDB37010303] ; National Natural Science Foundation of China[JCYJ-SHFY-2022-008] ; Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission)["31670748","31970576","31670802","32171269","32071195","31900934"] ; China Association for Science and Technology[2021 Sci Tech 03-28] ; National Postdoctoral Program for Innovative Talents[YESS20170198] ; [BX201700263]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000861134500003
出版者	CELL PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/238174
专题	生命科学与技术学院_PI研究组_庄敏组生命科学与技术学院_特聘教授组_陈勇组
通讯作者	Chen, Yong
作者单位	1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg SCICB, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China 4.Chinese Acad Sci, Shanghai Adv Res Inst, Zhangjiang Lab, Natl Facil Prot Sci Shanghai, Shanghai 201210, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 6.Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Shanghai 200237, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhao, Lijie,Huang, Naizhe,Mencius, Jun,et al. DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates[J]. ISCIENCE,2022,25(9).
APA	Zhao, Lijie.,Huang, Naizhe.,Mencius, Jun.,Li, Yanjing.,Xu, Ying.,...&Chen, Yong.(2022).DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates.ISCIENCE,25(9).
MLA	Zhao, Lijie,et al."DPY30 acts as an ASH2L-specific stabilizer to stimulate the enzyme activity of MLL family methyltransferases on different substrates".ISCIENCE 25.9(2022).