The activity of tissue transglutaminase is present in many cells and tissues but almost absent in leucocytes and lymphocytes. The present work describes the distribution of 5-methylcytosine along the bisulphite-converted promoter of the human tissue transglutaminase gene as being in an essentially repressed state. In this promoter, the chain-specific sequencing revealed the location of three CpG-rich domains whose methylation responds to an 'all or nothing' signal. While the CpGs of domain 1, at the 5'-end, and 2, in the mid-promoter, were fully methylated, those of domain 3, at the 3'-end, were fully unmethylated. Before the 5'-UTR sequence, from site+1 to site+67, also unmethylated, there was thus a striking contrast in the post-synthetic modification between the sequence, from -1594 to -436, containing domains 1 and 2, and the sequence, from -435 to -1, containing domain 3 with the core promoter.