CpG Islands and DNA Methylation

Methylated CpG dinucleotides at position 5 of cytosine are associated with transcriptional repression and an inactive chromatin conformation in mammals. CpG islands are nonmethylated, CpG-rich regions of ~1 kb that represent approximately 1% of the genome and contain promoters and deoxyribonucleic acid (DNA) replication origins.

Keywords: CpG islands; DNA methylation; DNA methyltransferases; chromatin; transcription

Figure 1. Three-dimensional structure of a double-stranded DNA fragment containing four methylated CpG dinucleotides. The methyl groups of the complementary methylated CpGs protrude into the major groove of the DNA molecule.
Figure 2. Examples of human genes with and without CpG islands. The diagrams show the distribution of CpGs across the 5¢ end of four human genes. The -globin and the aldose reductase (ADO) genes are associated with CpG islands, as is clearly shown by the high density of CpG dinucleotides around their 5¢ ends. In contrast, the frequency of CpGs at the 5¢ ends of the -globin and the 5-aminolevulinate synthase 2 (5-ALAS) genes is similar to the genome average. Vertical lines indicate CpGs. Boxes represent exons and arrows show the transcription initiation site. Only exon 1 of the ADO and 5-ALAS genes is shown.
Figure 3. Schematic representation of the chromatin structure of a CpG island. Vertical lines indicate CpGs. Most CpGs outside the islands are methylated (indicated by a black dot), while CpGs within the island remain nonmethylated. Transcription initiation from a nucleosome-free gap is indicated with an arrow. HS: sites of hypersensitivity to DNAase; MeCP: methyl CpG-binding protein; MBD: methyl CpG-binding domain.
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 References
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 Further Reading
    Antequera F and Bird A (1999) CpG islands as genomic footprints of promoters that are associated with replication origins. Current Biology 9: R661–R667.
    Bernstein BE, Meissner A and Lander ES (2007) The mammalian epigenome. Cell 128: 669–681.
    Bird A (1986) CpG-rich islands and the function of DNA methylation. Nature 321: 209–213.
    Freitag M, Hickey PC, Khlafallah TK, Read ND and Selker EU (2004) HP1 is essential for DNA methylation in Neurospora. Molecular Cell 13: 427–434.
    Hendrich B and Tweedie S (2003) The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends in Genetics 19: 269–277.
    Jones PA and Baylin SB (2007) The epigenomics of cancer. Cell 128: 683–692.
    Okano M, Bell DW, Haber DA and Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99: 247–257.
    Rollins RA, Haghighi F, Edwards JR et al. (2006) Large-scale structure of genomic methylation patterns. Genome Research 16: 157–163.
    Surani MA, Hayashi K and Hajkova P (2007) Genetic and epigenetic regulators of pluripotency. Cell 128: 747–762.
    Tazi J and Bird A (1990) Alternative chromatin structure at CpG islands. Cell 60: 909–920.
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How to Cite close
Antequera, Francisco(Dec 2007) CpG Islands and DNA Methylation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005027.pub2]