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Home arrow Health arrow DNA Modifications in the Brain. Neuroepigenetic Regulation of Gene Expression
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DNA METHYLATION AND ITS INFLUENCE ON DNA STRUCTURE AND INTERACTION WITH PROTEINS

We have been lucky to find unusual natural double-stranded DNA in AR9 bacteriophage of Bacillus brevis in which thymine is completely substituted by a typical RNA base, uracil. Basically, uracil is thymine lacking a methyl group. This bacteriophage DNA melted at significantly lower temperature compared with normal thymine- containing DNA of the equivalent base composition (Vanyushin, Belyaeva, et al., 1970). It became clear that methylation of cytosine residues is not indifferent to DNA structure: it stabilizes the double helix. Methylation of cytosine introduces a methyl group into an exposed position in the major groove of the DNA helix, and the binding of various proteins could be affected by such change (Razin & Riggs, 1980). It was well known that 5mC profoundly affects the binding of lac repressor to lac operator sequences, as well as the binding of bacterial restriction endonucleases to their recognition sites. The only question was whether eukaryotic cells use this mechanism to control regulatory protein binding to DNA. We have found a plant protein that binds specifically to regulatory elements of ribosomal RNA genes and showed that its binding is inhibited by in vitro methylation of cytosine residues in CCGG sites (Ashapkin, Antoniv, & Vanyushin, 1995). In many cases cytosine DNA methylation prohibits binding of specific nuclear proteins involved in transcription and other genetic processes. Conversely, there are proteins that bind specifically to methylated DNA sequences and arrange on DNA an entire ensemble of proteins controlling gene expression.

 
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