DNA methylation patterns: an additional level of information?

The DNA of many organisms contains modified bases such as 5-methylcytosine and 6-methyladenine, in addition to the four unmodified bases (reviewed by Razin and Szyf, Biochim. Biophys. Acta, 782, 331-342, 1984). A hallmark of DNA methylation in vertebrates is that a fraction of the CpG dinucleotide sequences is methylated at the 5 ' position (60-80%). The nonmethylated cytosines are distributed in a nonrandom fashion, generating a pattern of methylation that is gene and tissue specific (reviewed by Yisraeli, and Szyf, In DNA methylation: biochemistry and biological significance, Edited by Razin et al., Springer-Verlag, NY. pp. 353-378, 1984). The methylation pattern might therefore play an important role in shaping the differential identity of DNA during development. This nonrandom pattern begs the question: is methylation a passive mirror image of the gene expression profile of the genome, or does it represent an additional level of information? I believe that an understanding of the mechanisms that regulate the formation of methylation patterns is fundamental to assess the biological role of DNA methylation. This commentary proposes a model to explain the molecular mechanisms regulating the formation and inheritance of methylation patterns.