Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition

doi:10.1093/nar/gkv323

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 国家新药筛选中心

	Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition
	Kong, Xiangqian 1; Liu, Jian 2; Li, Lianchun 1; Yue, Liyan 1; Zhang, Lihong 2; Jiang, Hualiang1 ; Xie, Xin2 ; Luo, Cheng1
刊名	NUCLEIC ACIDS RESEARCH
	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.
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
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000355928800008
内容类型	期刊论文
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.