Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1

被引：35
作者：
Zandarashvili, Levani [1 ]
White, Mark A. [1 ]
Esadze, Alexandre [1 ]
Iwahara, Junji [1 ]
机构：
[1] Univ Texas Med Branch, Dept Biochem & Mol Biol, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA
来源：
FEBS LETTERS | 2015年 / 589卷 / 15期
关键词：
Protein-DNA interaction; CpG methylation; Egr-1; Crystallography; Fluorescence; PKC-EPSILON GENE; PROMOTER METHYLATION; BINDING DOMAIN; ZIF268; PROTEIN; RECOGNITION; SITES; SEQUENCE; REPRESSION; CHROMATIN; ISLANDS;
D O I：
10.1016/j.febslet.2015.05.022
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：
The inducible transcription factor Egr-1 binds specifically to 9-bp target sequences containing two CpG sites that can potentially be methylated at four cytosine bases. Although it appears that complete CpG methylation would make an unfavorable steric clash in the previous crystal structures of the complexes with unmethylated or partially methylated DNA, our affinity data suggest that DNA recognition by Egr-1 is insensitive to CpG methylation. We have determined, at a 1.4-angstrom resolution, the crystal structure of the Egr-1 zinc-finger complex with completely methylated target DNA. Structural comparison of the three different methylation states reveals why Egr-1 can recognize the target sequences regardless of CpG methylation. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：1748 / 1753
页数：6
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