Structural basis for Klf4 recognition of methylated DNA

被引：83

作者：

Liu, Yiwei ^{[1
]}

Olanrewaju, Yusuf Olatunde ^{[1
]}

Zheng, Yu ^{[2
]}

Hashimoto, Hideharu ^{[1
]}

Blumenthal, Robert M. ^{[3
,4
]}

Zhang, Xing ^{[1
]}

Cheng, Xiaodong ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA

[2] New England Biolabs Inc, Ipswich, MA 01938 USA

[3] Univ Toledo, Coll Med & Life Sci, Dept Med Microbiol & Immunol, Toledo, OH 43614 USA

[4] Univ Toledo, Coll Med & Life Sci, Program Bioinformat, Toledo, OH 43614 USA

来源：

NUCLEIC ACIDS RESEARCH | 2014年 / 42卷 / 08期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; CPG METHYLATION; MAMMALIAN DNA; PARTNER KAISO; TET PROTEINS; MOUSE; METHYLTRANSFERASE; 5-FORMYLCYTOSINE; 5-METHYLCYTOSINE; SEQUENCE;

D O I：

10.1093/nar/gku134

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Transcription factor Kruppel-like factor 4 (Klf4), one of the factors directing cellular reprogramming, recognizes the CpG dinucleotide (whether methylated or unmodified) within a specific G/C-rich sequence. The binding affinity of the mouse Klf4 DNA-binding domain for methylated DNA is only slightly stronger than that for an unmodified oligonucleotide. The structure of the C-terminal three Kruppel-like zinc fingers (ZnFs) of mouse Klf4, in complex with fully methylated DNA, was determined at 1.85 angstrom resolution. An arginine and a glutamate interact with the methyl group. By comparison with two other recently characterized structures of ZnF protein complexes with methylated DNA, we propose a common principle of recognition of methylated CpG by C2H2 ZnF proteins, which involves a spatially conserved Arg-Glu pair.

引用

页码：4859 / 4867

页数：9

共 47 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[2]

[Anonymous], EPIGENETIC MECH GENE

[3] Methylation-Dependent and -Independent Genomic Targeting Principles of the MBD Protein Family [J].

Baubec, Tuncay ;

Ivanek, Robert ;

Lienert, Florian ;

Schuebeler, Dirk .

CELL, 2013, 153 (02) :480-492

[4] CLONING AND SEQUENCING OF A CDNA-ENCODING DNA METHYLTRANSFERASE OF MOUSE CELLS - THE CARBOXYL-TERMINAL DOMAIN OF THE MAMMALIAN ENZYMES IS RELATED TO BACTERIAL RESTRICTION METHYLTRANSFERASES [J].

BESTOR, T ;

LAUDANO, A ;

MATTALIANO, R ;

INGRAM, V .

JOURNAL OF MOLECULAR BIOLOGY, 1988, 203 (04) :971-983

[5] Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso [J].

Buck-Koehntop, Bethany A. ;

Stanfield, Robyn L. ;

Ekiert, Damian C. ;

Martinez-Yamout, Maria A. ;

Dyson, H. Jane ;

Wilson, Ian A. ;

Wright, Peter E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (38) :15229-15234

[6] Integration of external signaling pathways with the core transcriptional network in embryonic stem cells [J].

Chen, Xi ;

Xu, Han ;

Yuan, Ping ;

Fang, Fang ;

Huss, Mikael ;

Vega, Vinsensius B. ;

Wong, Eleanor ;

Orlov, Yuriy L. ;

Zhang, Weiwei ;

Jiang, Jianming ;

Loh, Yuin-Han ;

Yeo, Hock Chuan ;

Yeo, Zhen Xuan ;

Narang, Vipin ;

Govindarajan, Kunde Ramamoorthy ;

Leong, Bernard ;

Shahab, Atif ;

Ruan, Yijun ;

Bourque, Guillaume ;

Sung, Wing-Kin ;

Clarke, Neil D. ;

Wei, Chia-Lin ;

Ng, Huck-Hui .

CELL, 2008, 133 (06) :1106-1117

[7] Detailed Structural-Functional Analysis of the Kruppel-like Factor 16 (KLF16) Transcription Factor Reveals Novel Mechanisms for Silencing Sp/KLF Sites Involved in Metabolism and Endocrinology [J].

Daftary, Gaurang S. ;

Lomberk, Gwen A. ;

Buttar, Navtej S. ;

Allen, Thomas W. ;

Grzenda, Adrienne ;

Zhang, Jinsan ;

Zheng, Ye ;

Mathison, Angela J. ;

Gada, Ravi P. ;

Calvo, Ezequiel ;

Iovanna, Juan L. ;

Billadeau, Daniel D. ;

Prendergast, Franklyn G. ;

Urrutia, Raul .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (10) :7010-7025

[8] The p120ctn-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides [J].

Daniel, JM ;

Spring, CM ;

Crawford, HC ;

Reynolds, AB ;

Baig, A .

NUCLEIC ACIDS RESEARCH, 2002, 30 (13) :2911-2919

[9] Coot:: model-building tools for molecular graphics [J].

Emsley, P ;

Cowtan, K .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :2126-2132

[10] Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: The enzyme modifies DNA in a non-processive manner and also methylates non-CpA sites [J].

Gowher, H ;

Jeltsch, A .

JOURNAL OF MOLECULAR BIOLOGY, 2001, 309 (05) :1201-1208

← 1 2 3 4 5 →