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

Abstract

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.

Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes

“…We explored an alternative hypothesis to explain the observed difference in mutation rates, which is based on the known phenomenon of hypermutability of methylated CpG dinucleotides to TpG (Coulondre et al 1978;Bird 1980;Britten et al 1988;Ponger et al 2001). As formulated, the differential-CpG-content hypothesis states that the difference in the CpG content is responsible for the observed mutation rate difference between exons and noncoding DNA.…”

Comparative isoschizomer profiling of cytosine methylation: The HELP assay

“…Cloning and sequencing of these HTFs revealed them to be (G+C)-and CpG dinucleotide-rich, allowing base compositional criteria to be created to predict presumably hypomethylated CpG islands (Gardiner-Garden and Frommer 1987). These criteria remain in use for genomic annotations today, defining sequences that tend to localize with transcription start sites, especially of genes active constitutively (Larsen et al 1992) or during embryogenesis (Ponger et al 2001).…”

Algorithms for CpG Islands Search: New Advantages and Old Problems

“…At least 25% of CpG islands are located far from gene promoters (Ponger et al, 2001). Although a lot of such CGIs overlap with repeats, (Graff et al, 1997;Ponger et al, 2001), other CGIs don't (Ponger et al, 2001;Hackenberg et al, 2006).…”

“…Although a lot of such CGIs overlap with repeats, (Graff et al, 1997;Ponger et al, 2001), other CGIs don't (Ponger et al, 2001;Hackenberg et al, 2006). They are often located near 3' gene region (Gardiner-Garden & Frommer, 1987) or within the gene (Hackenberg et al, 2006).…”

“…One can see that most of core promoter elements are GC-rich and could be a part of a CGI-associated promoter. CGIs are often located in 5' regions of genes, mostly overlapping with TSS (Gardiner-Garden & Frommer, 1987;Davuluri et al, 2001;Ponger et al, 2001), and participate in regulation of transcription initiation (Rozenberg et al, 2008). Housekeeping genes tend to have CGI promoter more frequently comparing to tissue-specific genes (Zhu et al, 2008).…”