A small proportion of the unmethylated genome (1%), the HpaII tiny fragment (HTF) fraction, has been observed in a wide range of species, by cutting with the methylation- sensitive HpaII restrictase. This differs from bluk DNA by being mostly unmethylated at the CpG dinucleotides, and a high G+C content, and they are frequently found as "islands" (Although they were called as CpG islands by Gardiner-Garden and Frommer before, the name was well established after this paper). Their distinguishable features are their very high CpG density, that is partially attributed to the elevated G+C content, but it could be due because of the absence of CpG deficiency - CpGs occur here at the expected composition frequency, and in other sequences it is perhaps lower because of the mutability of the 5mC to T by deamination. This has been observed as a very probable explanation of the different compositions seen in the human alpha-globin pseudogene in comparison with the functional copy, where only four out of 70 CpGs in the expressed gene still persist in the non- expressed pseudogene, and the remaining have been replaced by TpG and CpA. Another example of this mutability phenomenon has been seen in Neurospora 5S rDNA. This suggests that CpG islands have not lost their CpGs because they are mostly unmethylated. CpG islands are closely related to genes, and they have been associated both to housekeeping and to tissue- specific genes as well, where most islands include the 5' end of the transcribed region. Froman evolutionary point of view, on the other hand, invertebrate genes are found in unmethylated regions or CpG deficient, so it is reasonable to think that in the vertebrate lineage of the methylated fraction has grown at expenses of the old invertebrate sequences. As CpG islands are clearly associated with genes, they are helpful for locating and isolating genes of interest (different cloning strategies are mentioned in the paper). Existance of the CpG islands can be explained as accidental ("an inconsequential by-product of the evolution"), or they are essential, that is a more interesting possibility, because of their association with 5' regions, that suggests a role in the DNA - transcription factors interaction. Then, they could be crucial in the regulation of gene expression, and one form could be by rendering sequences through altered chromatin structures.
Bird, A. 1987. Trends Genet 3(12): 342-347
epigenetics
