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

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

doi:10.1016/j.febslet.2015.05.022

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

Journal Article · Tue May 19 00:00:00 EDT 2015 · FEBS Letters

DOI:https://doi.org/10.1016/j.febslet.2015.05.022· OSTI ID:1233751

Zandarashvili, Levani ^[1]; White, Mark A. ^[1]; Esadze, Alexandre ^[1]; Iwahara, Junji ^[1]

Univ. of Texas Medical Branch, Galveston, TX (United States)

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. In conclusion, structural comparison of the three different methylation states reveals why Egr–1 can recognize the target sequences regardless of CpG methylation.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH)

Grant/Contract Number:: R01‐GM107590; R01‐GM105931

OSTI ID:: 1233751

Journal Information:: FEBS Letters, Vol. 589, Issue 15; ISSN 0014-5793

Publisher:: Federation of European Biochemical SocietiesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 32 works

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59 BASIC BIOLOGICAL SCIENCES
5mC
5-methylcytosine
MBD
methyl-CpG-binding domain
RMSD
root-mean-square deviation
TAMRA
tetramethylrhodamine
Protein–DNA interaction
CpG methylation
Egr-1
Crystallography
Fluorescence

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

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