stable and consistent signal to activate the chromatin. Transient changes in cellular function and chromatin structure are not accompanied by changes in DNA methylation. The relation between chromatin state and DNA methylation forms a molecular link through which environmental signals might alter DNA methylation in specific genes in postmitotic neurons. Environmental signals trigger cellular signaling pathways, the downstream consequence of which is activation of trans-acting factors, such as transcription factors. These trans-acting factors recruit HATs to the target gene resulting in increased histone acetylation, chromatin opening, and increased accessibility of the DNA to demethylases. Since methylation of cytosine is an extremely stable chemical bond on DNA, this modification will remain stable for years. For methylation signals to serve as stable markers, they should not be responsive to transient chromatin noise or short-term signals. The mechanism proposed here also allows for a reversal of the methylation marker by a similar intense change in chromatin structure later in life.99,110 This model has 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
