Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition
文献类型：期刊论文
| 作者 | Kong, Xiangqian1; Liu, Jian2; Li, Lianchun1; Yue, Liyan1; Zhang, Lihong2; Jiang, Hualiang1 ; Xie, Xin2; Luo, Cheng1
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| 刊名 | NUCLEIC ACIDS RESEARCH
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| 出版日期 | 2015-05-19 |
| 卷号 | 43期号:9页码:4381-4392 |
| ISSN号 | 0305-1048 |
| DOI | 10.1093/nar/gkv323 |
| 文献子类 | Article |
| 英文摘要 | The POU family transcription factor Oct4 plays pivotal roles in regulating pluripotency and somatic cell reprogramming. Previous studies have indicated an important role for major groove contacts in Oct4-DNA recognition; however, the contributions of the RK motif in the POUh domain and the linker segment joining the two DNA-binding domains remain poorly understood. Here, by combining molecular modelling and functional assays, we find that the RK motif is essential for Oct4-DNA association by recognizing the narrowed DNA minor groove. Intriguingly, computational simulations reveal that the function of the RK motif may be finely tuned by H-bond interactions with the partially disordered linker segment and that breaking these interactions significantly enhances the DNA binding and reprogramming activities of Oct4. These findings uncover a self-regulatory mechanism for specific Oct4-DNA recognition and provide insights into the functional crosstalk at the molecular level that may illuminate mechanistic studies of the Oct protein family and possibly transcription factors in the POU family. Our gain-of-function Oct4 mutants might also be useful tools for use in reprogramming and regenerative medicine. |
| WOS关键词 | PROTEIN-DNA RECOGNITION ; TRANSCRIPTION FACTOR OCT-1 ; NUCLEIC-ACID STRUCTURES ; POU-DOMAIN PROTEINS ; MINOR-GROOVE ; BINDING SPECIFICITY ; COGNATE SITES ; FACTORS SOX2 ; STEM-CELLS ; I-POU |
| 资助项目 | Ministry of Science and Technology of China[2015CB910304] ; Ministry of Science and Technology of China[2015CB964503] ; Hi-Tech Research and Development Program of China[2012AA020302] ; Chinese Academy of Sciences[XDA01040301] ; Chinese Academy of Sciences[XDA01040305] ; National Natural Science Foundation of China[31371511] ; National Natural Science Foundation of China[81425024] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[21472208] ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2014ZX09507002] ; National Science and Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2013ZX09507-004] ; project of State Key Laboratory of Toxicology and Medical Countermeasures (Academy of Military Medical Science)[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000355928800008 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276524]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物发现与设计中心 |
| 通讯作者 | Luo, Cheng |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Kong, Xiangqian,Liu, Jian,Li, Lianchun,et al. Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition[J]. NUCLEIC ACIDS RESEARCH,2015,43(9):4381-4392. |
| APA | Kong, Xiangqian.,Liu, Jian.,Li, Lianchun.,Yue, Liyan.,Zhang, Lihong.,...&Luo, Cheng.(2015).Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition.NUCLEIC ACIDS RESEARCH,43(9),4381-4392. |
| MLA | Kong, Xiangqian,et al."Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition".NUCLEIC ACIDS RESEARCH 43.9(2015):4381-4392. |
入库方式： OAI收割
来源：上海药物研究所
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