Determinants of CpG islands: Expression in early embryo and isochore structure

In an attempt to understand the origin of CpG islands (CGIs) in mammalian g enomes, we have Studied their location and structure according to the expre ssion pattern of genes and to the G + C content of isochores in which they are embedded. We show that CGIs located over the transcription start site ( named start CGIs) are very different structurally from the others (named no -start CGIs): (1) 61.6% of the no-start CGIs are due to repeated sequences (79% are due to Alus), whereas only 5.6% of the start CGIs are due to Such repeats; (2) start CGIs are longer and display a higher CpGo/e ratio and G + C level than no-start CGIs. The frequency of tissue-specific genes associ ated to a start CGI varies according to the genomic G + C content, from 25% in G + C-poor isochores to 64% in G + C-rich isochores. Conversely, the fr equency of housekeeping genes associated to a start CGI (90%) is independen t of the isochore context. Interestingly, the structure of start CGIs is ve ry similar for tissue-specific and housekeeping genes. Moreover, 93% of gen es expressed in early embryo are found to exhibit a CpG island over their t ranscription start point. These observations are consistent with the hypoth esis that the occurrence of these CGIs is the consequence of gene expressio n at this stage, when the methylation pattern is installed.