Open AccessSequence Dependent Effects of CpG Cytosine Methylation
Author(s) -
Lefebvre Anne,
Mauffret Olivier,
Antri Saïd El,
Monnot Monique,
Lescot Elie,
Fermandjian Serge
Publication year - 1995
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1995.0445k.x
Subject(s) - cpg site , cytosine , oligonucleotide , methylation , dna methylation , chemistry , dna , stereochemistry , biophysics , crystallography , biochemistry , biology , gene , gene expression
The impact of cytosine methylation in the central CpG step of two closely related octanucleotide duplexes d(CATCGATG) 2 and d(CTTCGAAG) 2 was examined by 1 H‐NMR and 31 P‐NMR experiments, and a quantitative structural analysis was performed using the NOE‐derived distances, the sugar puckers and the ε torsion angles. The two starting oligonucleotides displayed a B‐DNA conformation with, however, significant local structure differences. Although the methylated oligonucleotides retained their B‐DNA conformation, different structural and thermal stability effects were observed. The magnitude of the methylation effects was to depend on the initial conformation of the CpG site, which is governed by the nature of the dinucleotide AT or TT located on the CpG flanks. As an example of sequence dependence, the methylation of CpG entailed larger conformational variation in d(CATCGATG) 2 than in d(CTTCGAAG) 2 . In this study, the 1 H and 31 P chemical‐shift parameters averred as extremely sensitive probes for detecting subtle conformational changes. Finally, our comparative results may aid our understanding of the structural and related biological effects produced by cytosine methylation in DNA.