Literature DB >> 25999311

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

Levani Zandarashvili1, Mark A White1, Alexandre Esadze1, Junji Iwahara2.   

Abstract

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.
Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Entities:  

Keywords:  CpG methylation; Crystallography; Egr-1; Fluorescence; Protein–DNA interaction

Mesh:

Substances:

Year:  2015        PMID: 25999311      PMCID: PMC4494898          DOI: 10.1016/j.febslet.2015.05.022

Source DB:  PubMed          Journal:  FEBS Lett        ISSN: 0014-5793            Impact factor:   4.124


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