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Structural basis for activity regulation of MLL family methyltransferases
Li, Yanjing1,2; Han, Jianming1,2; Zhang, Yuebin3; Cao, Fang4; Liu, Zhijun1,2; Li, Shuai5; Wu, Jian1,2; Hu, Chunyi1,2; Wang, Yan1,2; Shuai, Jin1,2; Chen, Juan1,2; Cao, Liaoran3; Li, Dangsheng6; Shi, Pan7; Tian, Changlin7,8,9; Zhang, Jian5; Dou, Yali4; Li, Guohui3; Chen, Yong1,2; Lei, Ming1,2
2016-02-25
发表期刊NATURE
摘要The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases.
文章类型Article
WOS标题词Science & Technology
DOI10.1038/nature16952
关键词[WOS]LINEAGE LEUKEMIA PROTEIN-1 ; HISTONE-MODIFYING GENES ; H3K4 METHYLATION ; SET1 FAMILY ; EXPRESSION ; COMPLEX ; DOMAIN ; RBBP5 ; ACTIVATION ; CHROMATIN
收录类别SCI
语种英语
项目资助者Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08010201 ; Ministry of Science and Technology of China(2013CB910402 ; Ministry of Science and Technology of China(2013CB910402 ; Ministry of Science and Technology of China(2013CB910402 ; Ministry of Science and Technology of China(2013CB910402 ; Ministry of Science and Technology of China(2013CB910402 ; Ministry of Science and Technology of China(2013CB910402 ; Ministry of Science and Technology of China(2013CB910402 ; Ministry of Science and Technology of China(2013CB910402 ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program' of China(2014ZX09507002-005) ; National Natural Science Foundation of China(31330040 ; National Natural Science Foundation of China(31330040 ; National Natural Science Foundation of China(31330040 ; National Natural Science Foundation of China(31330040 ; National Natural Science Foundation of China(31330040 ; National Natural Science Foundation of China(31330040 ; National Natural Science Foundation of China(31330040 ; National Natural Science Foundation of China(31330040 ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; Basic Research Project of Shanghai Science and Technology Commission(14JC1407200) ; National Institutes of Health(R01 GM082856) ; National Institutes of Health(R01 GM082856) ; National Institutes of Health(R01 GM082856) ; National Institutes of Health(R01 GM082856) ; National Institutes of Health(R01 GM082856) ; National Institutes of Health(R01 GM082856) ; National Institutes of Health(R01 GM082856) ; National Institutes of Health(R01 GM082856) ; Fundamental Research for the Central University(WK2340000064) ; Fundamental Research for the Central University(WK2340000064) ; Fundamental Research for the Central University(WK2340000064) ; Fundamental Research for the Central University(WK2340000064) ; Fundamental Research for the Central University(WK2340000064) ; Fundamental Research for the Central University(WK2340000064) ; Fundamental Research for the Central University(WK2340000064) ; Fundamental Research for the Central University(WK2340000064) ; XDB08030302) ; XDB08030302) ; XDB08030302) ; XDB08030302) ; XDB08030302) ; XDB08030302) ; XDB08030302) ; XDB08030302) ; 2013CB910401 ; 2013CB910401 ; 2013CB910401 ; 2013CB910401 ; 2013CB910401 ; 2013CB910401 ; 2013CB910401 ; 2013CB910401 ; 31470737 ; 31470737 ; 31470737 ; 31470737 ; 31470737 ; 31470737 ; 31470737 ; 31470737 ; 2012AA01A305 ; 2012AA01A305 ; 2012AA01A305 ; 2012AA01A305 ; 2012AA01A305 ; 2012AA01A305 ; 2012AA01A305 ; 2012AA01A305 ; 91430110) ; 91430110) ; 91430110) ; 91430110) ; 91430110) ; 91430110) ; 91430110) ; 91430110) ; 2012CB721002 ; 2012CB721002 ; 2012CB721002 ; 2012CB721002 ; 2012CB721002 ; 2012CB721002 ; 2012CB721002 ; 2012CB721002 ; 2011CB910400) ; 2011CB910400) ; 2011CB910400) ; 2011CB910400) ; 2011CB910400) ; 2011CB910400) ; 2011CB910400) ; 2011CB910400)
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000370690800028
引用统计
被引频次：159[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.hfcas.ac.cn:8080/handle/334002/22295
专题中科院强磁场科学中心
作者单位1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai,State Key Lab Mol Biol, 333 Haike Rd, Shanghai 201210, Peoples R China
2.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai 201204, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Liaoning, Peoples R China
4.Univ Michigan, Dept Pathol, Sch Med, 1301 Catherine, Ann Arbor, MI 48109 USA
5.Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Dept Pathophysiol,Key Lab Cell Differentiat & Apo, Shanghai 200025, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Informat Ctr Life Sci, Shanghai 200031, Peoples R China
7.Chinese Acad Sci, High Field Magnet Lab, Hefei 230031, Peoples R China
8.Univ Sci & Technol China, Natl Lab Phys Sci Microscale, Hefei 230026, Peoples R China
9.Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China
推荐引用方式
GB/T 7714		 Li, Yanjing,Han, Jianming,Zhang, Yuebin,et al. Structural basis for activity regulation of MLL family methyltransferases[J]. NATURE,2016,530(7591):447-+.
APA Li, Yanjing.,Han, Jianming.,Zhang, Yuebin.,Cao, Fang.,Liu, Zhijun.,...&Lei, Ming.(2016).Structural basis for activity regulation of MLL family methyltransferases.NATURE,530(7591),447-+.
MLA Li, Yanjing,et al."Structural basis for activity regulation of MLL family methyltransferases".NATURE 530.7591(2016):447-+.
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