CpG island

There are wide variations in features of individual chromosomes (eg, in gene number per Mb, SNP density, GC content, numbers of transposable elements and CpG islands, recombination rate). 

ISSA J p, OTTAVIANO Y L, CELANO P, HAMILTON S R, DAVIDSON N E and BAYLIN S B (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon , Nat Genet, 1, 536-40. 

Bastian, PJ, J Ellinger, LC Heukamp, P Kahl, SC Muller, and A von Rucker. 2007. Prognostic value of CpG island methylation of PTGS2, RAR-beta, EDNRB, and other gene loci in patients undergoing radical prostatectomy. Eur Urol 51(3) 665—674. 

Lin, X, M Tascilar, WH Lee et al. 2001. GSTP1 CpG island hypermethylation is responsible for the absence of GSTP1 expression in human prostate cancer cells. Am J Pathol 159 1815-1826. 

J. A. Engelman, X. L. Zhang, and M. P. Lisanti. Methylation of a CpG island in the 5 promoter region of the caveolin-1 gene in human breast cancer cell lines. FEBS Lett. 448 221-230 (1999). 

Choi, Y.C., Gu, W., Hecht, N.B., Feinberg, A.P., and Chae, C.B. (1996) Molecular cloning of mouse somatic and testis-specific H2B histone genes containing a methylated CpG island. DNA Cell Biol. 15, 495-504. 

Relationships between histone methylation and DNA methylation and histone acetyation and DNA methylation have been reported [191,314,315], A similar relationship may exist between poly(ADP ribosylated) HI and DNA methylation. Inhibition of poly(ADP-ribose) polymerase with 3-aminobenzamide increases the susceptibility of L929 mouse fibroblast nuclei to be methylated by endogenous DNA methyltransferases [316,317], Further, there is evidence that poly(ADP ribosylation) protects CpG islands located at the 5 end of housekeeping genes from methylation [318], Future studies will likely reveal an interesting dynamic relationship between histone methylation, histone acetylation, and histone poly(ADP-ribosylation). 

The methylation of DNA at CpG islands has also turned out to be an important regulator for cell development, the differentiated proteome and the regulation of cell survival [237,238]. Indeed the implications of this chemical modification have been linked to DNA accessibility, chromatin fluidity and cell transformation [239,240]. DNA methylation is required for genomic stability and believed to act as an inert epigenetic marker in germinal cells and preimplantation embryos [238]. Presumably, DNA methylation is required for the heritable transmission of chromatin structure, which prevents the expression of terminally silenced genes in differentiated tissues, and provides a host-defense mechanism against parasitic transposable elements [241]. 

Fig. 1. Dynamics of DNA methylation levels during mouse development. The methylation patterns of the oocyte and the rapidly demethylated after fertilization sperm create the combined methylation patterns in the early mouse zygote. During the first two to three cleavage divisions, the 5mC levels decrease further and stay low through the blastula stage. Post-implantation, the mouse embryo genome is methylated de novo the CpG islands remain mostly unmethylated. The primordial germ cells remain unmethylated. During gametogenesis specific parental (maternal or paternal) patterns of DNA methylation are established at imprinted loci (for further details see Refs. [13, 14]) (re-drawn from Ref [4]).

The fact that CpG dinucleotides exist in an unmethylated state in CpG islands is amazing, given that the frequency of CpGs in such islands is six to ten times higher than in bulk DNA [17] (Table 1). A great deal of investigation has been and is being... 

CpG island downstream of Initiation sites - methylation does not effect transcription... 

Fig. 2. Distribution of methylated CpGs in genomic DNA and their effect on transcription. 70-80% of all CpG dinucleotides are methylated in vertebrate genomes. mCpGs (filled lollipops) are randomly distributed throughout the genome but are excluded from regions with unusually high CpG density—CpG islands [16,17]. Most of the CpG islands are associated with gene promoters and maintained unmethylated (white lollipops) in all types of somatic cells. Aberrant methylation of CpG islands occurs in cancer cells and leads to silencing of tumor-suppressor and other essential genes [19-21].

CpG islands can remain methylation-free even when the associated gene is silent [23],... 

Finally, targeted active demethylation has been put forward as an explanation for the unmethylated state of CpG islands (Fig. 3e). In this model, features of active chromatin structure (e.g., histone hyperacetylation) cause active demethylation of associated sequences [43,44]. Based on a broad analysis of existing data, Szyf... 

---