DOI | 10.1038/s41586-020-2097-z
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| Phase separation directs ubiquitination of gene-body nucleosomes |
| Zhang, Wenjuan1; Tarutani, Airi2; Newell, Kathy L.3; Murzin, Alexey G.1; Matsubara, Tomoyasu4; Falcon, Benjamin1; Vidal, Ruben3; Garringer, Holly J.3; Shi, Yang1; Ikeuchi, Takeshi5; Murayama, Shigeo4; Ghetti, Bernardino3; Hasegawa, Masato2; Goedert, Michel1; Scheres, Sjors H. W.1
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| 2020-02-12
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发表期刊 | NATURE
![](/C666/image/waiting.gif) |
ISSN | 0028-0836
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EISSN | 1476-4687
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出版年 | 2020
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卷号 | 579期号:7800页码:592-+ |
文章类型 | Article
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语种 | 英语
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国家 | Austria; USA |
英文关键词 | The yeast E3 ligase Bre1 forms a core-shell condensate with the scaffold protein Lge1, implicating liquid-liquid phase separation as a mechanism in the ubiquitination of histone H2B along gene bodies.
The conserved yeast E3 ubiquitin ligase Bre1 and its partner, the E2 ubiquitin-conjugating enzyme Rad6, monoubiquitinate histone H2B across gene bodies during the transcription cycle(1). Although processive ubiquitination might-in principle-arise from Bre1 and Rad6 travelling with RNA polymerase II2, the mechanism of H2B ubiquitination across genic nucleosomes remains unclear. Here we implicate liquid-liquid phase separation(3) as the underlying mechanism. Biochemical reconstitution shows that Bre1 binds the scaffold protein Lge1, which possesses an intrinsically disordered region that phase-separates via multivalent interactions. The resulting condensates comprise a core of Lge1 encapsulated by an outer catalytic shell of Bre1. This layered liquid recruits Rad6 and the nucleosomal substrate, which accelerates the ubiquitination of H2B. In vivo, the condensate-forming region of Lge1 is required to ubiquitinate H2B in gene bodies beyond the +1 nucleosome. Our data suggest that layered condensates of histone-modifying enzymes generate chromatin-associated '
reaction chambers'
, with augmented catalytic activity along gene bodies. Equivalent processes may occur in human cells, and cause neurological disease when impaired.
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领域 | 地球科学
; 气候变化
; 资源环境
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收录类别 | SCI-E
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WOS记录号 | WOS:000519162500009
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WOS关键词 | H2B UBIQUITYLATION
; HISTONE H2B
; MONOUBIQUITINATION
; BRE1
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WOS类目 | Multidisciplinary Sciences
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WOS研究方向 | Science & Technology - Other Topics
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引用统计 |
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文献类型 | 期刊论文
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条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281114
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专题 | 地球科学 资源环境科学 气候变化
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作者单位 | 1.MRC Lab Mol Biol, Cambridge, England; 2.Tokyo Metropolitan Inst Med Sci, Dept Dementia & Higher Brain Funct, Tokyo, Japan; 3.Indiana Univ Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA; 4.Tokyo Metropolitan Inst Gerontol, Dept Neuropathol, Tokyo, Japan; 5.Niigata Univ, Dept Mol Genet, Brain Res Inst, Niigata, Japan
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推荐引用方式 GB/T 7714 |
Zhang, Wenjuan,Tarutani, Airi,Newell, Kathy L.,et al. Phase separation directs ubiquitination of gene-body nucleosomes[J].
NATURE,2020,579(7800):592-+.
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APA |
Zhang, Wenjuan.,Tarutani, Airi.,Newell, Kathy L..,Murzin, Alexey G..,Matsubara, Tomoyasu.,...&Scheres, Sjors H. W..(2020).Phase separation directs ubiquitination of gene-body nucleosomes.NATURE,579(7800),592-+.
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MLA |
Zhang, Wenjuan,et al."Phase separation directs ubiquitination of gene-body nucleosomes".NATURE 579.7800(2020):592-+.
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