CpG site
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "CpG_site".

Cytosine
Cytosine
Phosphate
Phosphate
Guanine
Guanine

CpG sites are regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence of bases along its length. "CpG" stands for cytosine and guanine separated by a phosphate, which links the two nucleosides together in DNA. The "CpG" notation is used to distinguish a cytosine followed by guanine from a cytosine base paired to a guanine.

Cytosines in CpG dinucleotides are methylated by DNA methyltransferases in many eukaryotic organisms to form 5-methylcytosine. It can be noted that mammals methylate 70%-80% of CpG cytosines.[1]

Un-methylated CpG sites can be detected by macrophages in humans. This is used to detect intracellular bacterial DNA from pathogens.

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Frequency in vertebrates

CpG dinucleotides have long been observed to occur with a much lower frequency in the sequence of vertebrate genomes than would be expected due to random chance. For example, in a genome with 42% GC content (like the human genome), a pair of nucleotides consisting of cytosine followed by guanine would be expected to occur 0.21 * 0.21 = 4.41% of the time. The frequency of CpG dinucleotides in human genomes is 1% — less than one quarter of the expected frequency. Scarano et al. proposed that the CpG deficiency is due to an increased vulnerability of methylcytosines to transition mutation in genomes with CpG cytosine methylation.[2]

CpG islands

There are regions of the DNA that have a higher concentration of CpG sites, known as CpG islands. Many genes in mammalian genomes have CpG islands associated with the start of the gene.[3] Because of this, the presence of a CpG island is used to help in the prediction and annotation of genes. These increased concentrations of CpGs might be associated with the decreased methylation of cytosines often observed in CpG islands — this could result in a reduced vulnerability to transition mutations and, as a consequence, a higher equilibrium density of CpGs surviving.

Methylation, silencing, and cancer

Methylation of CpG sites within the promoters of genes can lead to their silencing, a feature found in a number of human cancers (for example the silencing of tumor suppressor genes). In contrast, the hypomethylation of CpG sites has been associated with the over-expression of oncogenes within cancer cells.[4]

See also

References

  1. ^ Jabbari K, Bernardi G (2004). "Cytosine methylation and CpG, TpG (CpA) and TpA frequencies". Gene 333: 143–9. doi:10.1016/j.gene.2004.02.043. PMID 15177689. 
  2. ^ Scarano E, Iaccarino M, Grippo P, Parisi E (1967). "The heterogeneity of thymine methyl group origin in DNA pyrimidine isostichs of developing sea urchin embryos". Proc. Natl. Acad. Sci. USA 57 (5): 1394–400. doi:10.1073/pnas.57.5.1394. PMID 5231746. 
  3. ^ (2005) Genetics: Analysis of Genes and Genomes, 6, Missisauga: Jones and Bartlett Publishers Canada, 477. ISBN 0-7637-1511-5. 
  4. ^ Jones PA, Laird PW (1999). "Cancer epigenetics comes of age". Nat. Genet. 21 (2): 163–7. doi:10.1038/5947. PMID 9988266. 
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