Gene Methylation Patterns and Expression

Three basic approaches have been employed in the study of the effect of DNA methylation of particular genes on their expression. One approach uses chemicals that cause demethylation (e.g., 5-azacytidine [5-aza-C]), thereby changing the methylation pattern of the cellular genome (see Chapter 9). Using the proper selection techniques, the expression of particular genes following hypomethylation can be assayed. This method is limited, however, by the fact that the sequences of interest may not undergo hypomethylation in a fashion that will mimic normal developmental processes. Using the second approach, genes can be methylated in vitro and can be introduced into cellular genomes, thus allowing the study of the effect of methylation at specific sites on gene expression (see Chapter 8). Again, it remains unclear how relevant the results of such experiments are to the processes occurring in vivo. The third approach involves careful observation of the naturally occurring variations in the methylation pattern of a particular gene in various tissues. A large number of genes have been studied using this approach. In this chapter, the available data is brought together and discussed in an attempt to obtain a general concept of the pattern of methylation of eukaryotic genes and to examine the interrelationship between DNA methylation patterns of particular genes and their expression.