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Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr‐1
Author(s) -
Zandarashvili Levani,
White Mark A.,
Esadze Alexandre,
Iwahara Junji
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.05.022
Subject(s) - cpg site , dna methylation , methylation , dna , differentially methylated regions , transcription factor , biology , transcription (linguistics) , epigenetics of physical exercise , illumina methylation assay , zinc finger , microbiology and biotechnology , rna directed dna methylation , chemistry , genetics , gene , gene expression , linguistics , philosophy
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‐Å 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.