Chromatin Structure

While promoter methylation is a conspicuous mark of gene silencing, DNA methylation is certainly not the only mechanism involved. Many invertebrates achieve gene silencing without DNA methylation at all and even in mammals not all silenced genes become methylated. Rather, DNA methylation in general represents one of the last steps in a chain of events leading to stable gene repression (Figure 8.7) and often serves to fix the state of a gene silenced by other means. It has therefore been considered a 'lock-in' mechanism, but - to keep with the metaphor -in some cases, as during X-inactivation, the door seems already to have been locked by other mechanisms and DNA methylation acts as an additional bolt. Importantly, the chain of events presented in Figure 8.7 is not a gradual transition. Rather, feedback and feed-forward mechanisms tend to enforce and stabilize the active and inactive states of a gene.





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