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CpG island



    CpG islands are genomic regions that contain a high frequency of CG dinucleotides. In mammalian genomes, CpG islands are typically 300-3,000 base pairs in length. They are in and near approximately 40% of promoters of mammalian genes (about 70% in human promoters).[1][2] The "p" in CpG notation refers to the phosphodiester bond between the cytosine and the guanine.

Additional recommended knowledge

The usual formal definition of a CpG island is a region with at least 200 bp and with a GC percentage that is greater than 50% and with an observed/expected CpG ratio that is greater than 60%.[3] Another recent study revised the rules of CpG island prediction in order to exclude other GC-rich genomic sequences such as Alu repeats. Based on an extensive search on the complete sequences of human chromosomes 21 and 22, DNA regions >500 bp with a GC content >55% and observed CpG/expected CpG of 0.65 were more likely to be the true CpG islands associated with the 5' regions of genes.[4]

CpG islands are characterized by CpG dinucleotide content of at least 60% of that which would be statistically expected (~4-6%), whereas the rest of the genome has much lower CpG frequency (~1%), a phenomenon called CG suppression. Unlike CpG sites in the coding region of a gene, in most instances, the CpG sites in the CpG islands of promoters are unmethylated if genes are expressed. This observation led to the speculation that methylation of CpG sites in the promoter of a gene may inhibit the expression of a gene. Methylation is central to imprinting alongside histone modifications.[5]

CpG islands typically occur at or near the transcription start site of genes, particularly housekeeping genes, in vertebrates.[2] Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the cytosines in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time methylated cytosines tend to turn into thymines because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some reason, perhaps having to do with the regulation of gene expression.

See also

References

  1. ^ Fatemi M, Pao MM, Jeong S, Gal-Yam EN, Egger G, Weisenberger DJ, Jones PA (2005). "Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level". Nucleic Acids Res 33 (20): e176. PMID 16314307.
  2. ^ a b Saxonov S, Berg P, Brutlag DL (2006). "A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters". Proc Natl Acad Sci USA 103 (5): 1412-1417. PMID 16432200.
  3. ^ Gardiner-Garden M, Frommer M (1987). "CpG islands in vertebrate genomes". Journal of molecular biology 196 (2): 261. PMID 3656447.
  4. ^ Takai D, Jones PA (2002). "Comprehensive analysis of CpG islands in human chromosomes 21 and 22.". Proc Natl Acad Sci USA 99 (6): 3740-5. PMID 11891299.
  5. ^ Feil R, Berger F (2007). "Convergent evolution of genomic imprinting in plants and mammals". Trends Genet 23 (4): 192-199. PMID 17316885.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "CpG_island". A list of authors is available in Wikipedia.
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