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Methylated DNA

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The genes of organisms, like plants and animals, offer the blueprint, not only to build the organism anew from a seed or fertilized egg cell, but also to adapt the living organism to its habitat and life experience. For example, a type of tree growing in an arid or wet region will adapt expression of its genes for root growth optimal to circumstances. A child living on a scarce or abundant diet or with little or much physical activity will adapt body growth accordingly. The needed, life time adaptation requires an individual's change in gene expression. This change is the subject of epigenetics. One control element in epigenetics is that cytosine bases of an organism's DNA become methylated in a chemical reaction in which a hydrogen atom is replaced by a methyl group (CH3). Another control element involves hydroxymethylation of cytosine bases where the H atom is replaced by a hydroxymethyl group (CH2OH); hydroxymethylation arises mainly in brain tissue. DNA methylation and hydroxymethylation patterns depend on an organism's individual history; aberrant patterns can be the cause of diseases, for example, of certain cancers. It is known that the proteins involved in gene expression can recognize methylated sites of DNA and, thereby, direct gene expression; DNA methylation also affects the packing of DNA in the chromosomes. However, methylation and hydroxymethylation may also affect gene expression directly; indeed, experiment and computational modeling with NAMD suggest this as an intriguing third way for methylation and hydroxymethylation to regulate gene expression. Methylation is shown, as reported recently, to make it more difficult to separate the two strands of DNA, as is necessary during gene expression. An earlier experimental-computational study had revealed already that methylated DNA can pass narrow synthetic nanopores more readily than unmethylated DNA can (see the Feb 2009 highlight). A recent experimental-computational study has shown that also in the case of hydroxymethylation mechanical properties of DNA become altered, namely, the forces needed to separate the two strands of DNA are strongly affected. The three experimental-computational findings advance our understanding of methylation and hydroxymethylation-based epigenetics and of how our body adapts to our life style and environment. More on our DNA methylation and hydroxymethylation website.