CpG islands in human X-inactivation

Sequence comparison analyses have been carried out for 19 genes escaping X-inactivation versus 73 genes subject to X-inactivation, and 100 randomly chosen X chromosome genes versus 100 randomly chosen autosomal genes. The coding sequence of the genes and their upstream and downstream flanking sequences were investigated using a series of windows (1 kb, 2 kb, 5 kb, 10 kb and 100 kb). No significant difference in number of LINE-L1 elements was observed in genes escaping X-inactivation compared to genes subject to X-inactivation. This result, therefore, does not support the suggestion that lack of LINE repeat elements is a key factor for genes escaping X-inactivation. However, significantly reduced numbers of CpG islands and SINE MIR elements were found to be associated with genes escaping X-inactivation. Compared to genes known to be inactivated, genes escaping X-inactivation were observed to have fewer CpG islands, particularly within the 2 kb upstream flanking sequence close to the coding region. The results suggest that CpG islands may play a role in the process of X-inactivation by providing sufficient DNA methylation targets for the maintenance of X-inactivation. Lack of CpG islands may be a major reason for genes escaping X-inactivation regulation.