Patterns of DNA methylation at CpG dinucleotides and their relations with gene 
expression are complex. Methylation-free CpG clusters, so-called HTF islands, 
are most often associated with the promoter regions of housekeeping genes, 
whereas genes expressed in a single-cell type are usually deficient in these 
sequences. However, in the human carbonic anhydrase (CA) gene family, both the 
ubiquitously expressed CAII and the muscle specific CAIII appear to have such 
CpG islands although erythrocyte-specific CAI does not. The CAII island is 
quantitatively more CpG rich than that of CAIII, with a CpG:GpC ratio of 0.94 
compared with 0.82 for CAIII. Estimation of CpG:GpC ratios in the 
proximal-promoter regions of 44 vertebrate genes suggest that 40% of genes with 
tissue-specific or limited tissue distribution may show methylation-free CpG 
clusters in their promoter regions. In many cases the CpG:GpC ratio is less than 
that found in housekeeping genes and this may reflect variation in the 
interaction of CpG clusters with regulatory factors that define different 
patterns of tissue expression.