Determinants of CpG Islands: Expression in Early Embryo and Isochore Structure

In an attempt to understand the origin of CpG islands (CGIs) in mammalian genomes, we have studied their location and structure according to the expression 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 associated 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 frequency of housekeeping genes associated to a start CGI (90%) is independent of the isochore context. Interestingly, the structure of start CGIs is very similar for tissue-specific and housekeeping genes. Moreover, 93% of genes expressed in early embryo are found to exhibit a CpG island over their transcription start point. These observations are consistent with the hypothesis that the occurrence of these CGIs is the consequence of gene expression at this stage, when the methylation pattern is installed.