Methylation Status of CpG Sites in the Mouse and Human CFTR Promoters

To determine whether a relationship exists between DNA methylation and CFTR gene expression, we investigated the methylation status of CpG sites in the mouse and human CFTR promoters. Tissues and previously characterized cell lines that vary with respect to CFTR expression were selected for analysis using the methylation sensitive restriction endonuclease Hha I. We find that CpG sites are not methylated in high and low CFTR-expressing cell lines, whereas in the very low or non-CFTR-expressing cell lines, the CpG sites are partially or completely methylated. However, none of these sites were methylated in any of the tissues examined irrespective of the state of CFTR expression. Therefore, we conclude that the CFTR promoter belongs to the class of CpG-rich promoters in which the associated CpG sites are not methylated in tissues and that an inverse correlation between methylation and CFTR expression can only be found in cell lines.