Despite their abundance of methylatable cytosines, CpG islands are thought to be unmethylated in all tissues regardless of gene expression, except for imprinted genes and genes located on the inactive X chromosome. This implies'that CpG island methylation could not play a role in establishing and maintaining tissue-specific gene expression. However, in a preliminary analysis of four different tissue/cell types, we identified a gene, SHANK3, whose CpG island methylation and expression patterns appear tissue type- specific and evolutionarily conserved. I hypothesize that CpG island methylation helps to establish and maintain the tissue-specific expression pattern of SHANK3. This study of SHANK3, an essential gene for normal brain development, will provide a specific example of how CpG island methylation contributes to tissue-specific gene expression patterns and, based on our genome-wide analysis of CpG islands, may be widely applicable to hundreds of additional tissue-specific genes.
