title: Structural insights into Paf1 complex assembly and histone binding.
abstract: The highly conserved Paf1 complex (PAF1C) plays critical roles in RNA polymerase II transcription elongation and in the regulation of histone modifications. It has also been implicated in other diverse cellular activities, including posttranscriptional events, embryonic development and cell survival and maintenance of embryonic stem cell identity. Here, we report the structure of the human Paf1/Leo1 subcomplex within PAF1C. The overall structure reveals that the Paf1 and Leo1 subunits form a tightly associated heterodimer through antiparallel beta-sheet interactions. Detailed biochemical experiments indicate that Leo1 binds to PAF1C through Paf1 and that the Ctr9 subunit is the key scaffold protein in assembling PAF1C. Furthermore, we show that the Paf1/Leo1 heterodimer is necessary for its binding to histone H3, the histone octamer, and nucleosome in vitro. Our results shed light on the PAF1C assembly process and substrate recognition during various PAF1C-coordinated histone modifications.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, 94 Weijin Road, Tianjin 300071, China, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China and Synergetic Innovation Center of Chemical Science and Engineering, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Chu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qin
authors.forename: Huisha
authors.initials: H
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Li
authors.forename: Xingqiao
authors.initials: X
authors.lastname: Xie
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Yuequan
authors.initials: Y
authors.lastname: Shen
authors.forename: Jiafu
authors.initials: J
authors.lastname: Long
mesh_terms: D019281:Dimerization; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006657:Histones; C506154:LEO1 protein, human; D009687:Nuclear Proteins; C501972:PAF1 protein, human; D021122:Protein Subunits; D014157:Transcription Factors
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