A proven role for methylation

Cytosine methylation has been proposed to modulate tissue-specific expression, but compelling evidence has been hard to find. In an Advanced Online Publication in Nature Genetics, Bernard Futscher and colleagues describe a clear example of cell type-specific gene regulation by DNA methylation (Nat Genet 2002, DOI:10.1038/ng886).

Futscher et al. studied the maspin gene SERPINB5, expression of which is restricted to epithelial cells, and show, by bisulfite sequencing, that CpG sites in the SERPINB5 promoter were unmethylated in maspin-positive cells. Chromatin immunoprecipitation experiments using antibodies specific for acetylated histones H3 and H4 revealed depleted acetylation in methylated SERPINB5-negative cells. Demethylation of the promoter by DNA methyltransferase inhibitors reactivated SERPINB5 expression.

These results indicate a clear relationship between cytosine methylation, histone acetylation and tissue-specific regulation.