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, Futscher et al. describe a clear example of cell type-specific gene regulation by DNA methylation (Nature Genetics 20 May 2002, DOI:10.1038/ng886). They 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.