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

Levani Zandarashvili; Mark A. White; Alexandre Esadze; Junji Iwahara

doi:10.1016/j.febslet.2015.05.022

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

Levani Zandarashvili, Mark A. White, Alexandre Esadze, Junji Iwahara

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

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.

Original language	English (US)
Article number	37178
Pages (from-to)	1748-1753
Number of pages	6
Journal	FEBS Letters
Volume	589
Issue number	15
DOIs	https://doi.org/10.1016/j.febslet.2015.05.022
State	Published - Jul 3 2015

Keywords

CpG methylation
Crystallography
Egr-1
Fluorescence
Protein-DNA interaction

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2015.05.022

Cite this

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

abstract = "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-{\AA} 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.",

keywords = "CpG methylation, Crystallography, Egr-1, Fluorescence, Protein-DNA interaction",

author = "Levani Zandarashvili and White, {Mark A.} and Alexandre Esadze and Junji Iwahara",

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T1 - Structural impact of complete CpG methylation within target DNA on specific complex formation of the inducible transcription factor Egr-1

AU - Zandarashvili, Levani

AU - White, Mark A.

AU - Esadze, Alexandre

AU - Iwahara, Junji

PY - 2015/7/3

Y1 - 2015/7/3

N2 - 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.

AB - 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.

KW - CpG methylation

KW - Crystallography

KW - Egr-1

KW - Fluorescence

KW - Protein-DNA interaction

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

Abstract

Keywords

ASJC Scopus subject areas

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