Phase separation directs ubiquitination of gene-body nucleosomes

doi:10.1038/s41586-020-2097-z

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2097-z
	Phase separation directs ubiquitination of gene-body nucleosomes
	Zhang, Wenjuan 1; Tarutani, Airi 2; Newell, Kathy L.3; Murzin, Alexey G.1; Matsubara, Tomoyasu 4; Falcon, Benjamin 1; Vidal, Ruben 3; Garringer, Holly J.3; Shi, Yang 1; Ikeuchi, Takeshi 5; Murayama, Shigeo 4; Ghetti, Bernardino 3; Hasegawa, Masato 2; Goedert, Michel 1; Scheres, Sjors H. W.1
	2020-02-12
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	579 期号:7800 页码:592-+
文章类型	Article
语种	英语
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.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000519162500009
WOS关键词	H2B UBIQUITYLATION ; HISTONE H2B ; MONOUBIQUITINATION ; BRE1
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281114
专题	地球科学资源环境科学气候变化
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
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-+.
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-+.
MLA	Zhang, Wenjuan,et al."Phase separation directs ubiquitination of gene-body nucleosomes".NATURE 579.7800(2020):592-+.