important implications on our understanding of how environmental signals, such as variations in maternal care, might stably alter glucocorticoid gene expression. DNA methylation marks genes for silencing by a number of mechanisms. The first mechanism is indirect and links DNA methylation to inactive chromatin structure. A region of methylated DNA juxtaposed to regulatory regions of genes attracts different members of a family of methylated DNA binding proteins, such as methylCpG-binding protein, MeCP2, which recruits HDACs105,106 and histone methyltransferases111 to methylated genes.91,112 This results in a modification of chromatin around the gene precipitating an inactive chromatin structure. A different mechanism, which is relevant to our discussion here, involves direct interference of a specific methylated CpG residing within a response element for a transcription factor with the interaction of a transcription factor, such as the inhibition of binding of cMyc to its response element when it is methylated.113 Essentially, the methylated cytosine serves as a mutation of the recognition element, functionally reducing the binding affinity of the response element for its transcription factor. A third mechanism involves a combination of binding of a methylated DNA binding protein and inhibition of activity of a transcription factor.114 While the first mechanism is dependent on
