CpG sites or CG sites are regions of DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 where a cytosine

Cytosine

Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...

 nucleotide

Nucleotide

Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

 occurs next to a guanine

Guanine

Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...

 nucleotide in the linear sequence

DNA sequence

The sequence or primary structure of a nucleic acid is the composition of atoms that make up the nucleic acid and the chemical bonds that bond those atoms. Because nucleic acids, such as DNA and RNA, are unbranched polymers, this specification is equivalent to specifying the sequence of...

 of base

Base pair

In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

s along its length. "CpG" is shorthand for "—C—phosphate—G—", that is, cytosine and guanine separated by only one phosphate

Phosphate

A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...

; phosphate links any two nucleoside

Nucleoside

Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...

s together in DNA. The "CpG" notation is used to distinguish this linear sequence from the CG base-pairing

Base pair

In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

 of cytosine and guanine.

Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosine

5-Methylcytosine

5-Methylcytosine is a methylated form of the DNA base cytosine that may be involved in the regulation of gene transcription. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered .In the figure on the right, a methyl group, is...

. In mammal

Mammal

Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s, methylating the cytosine within a gene can turn the gene off, a mechanism that is part of a larger field of science studying gene regulation that is called epigenetics

Epigenetics

In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...

. Enzymes that add a methyl group are called DNA methyltransferase

DNA methyltransferase

In biochemistry, the DNA methyltransferase family of enzymescatalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions...

s.

In mammals, 70% to 80% of CpG cytosines are methylated.

Unmethylated CpG sites can be detected by Toll-Like Receptor 9 (TLR 9) on plasmacytoid dendritic cell

Plasmacytoid dendritic cell

Plasmacytoid dendritic cells are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs. They constitute...

s and B cell

B cell

B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

s in humans. This is used to detect intracellular viral, fungal, and bacterial pathogen DNA.

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 the human genome, which has a 42% GC content, 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 spontaneously deaminate to thymine in genomes with CpG cytosine methylation.

CpG islands

There are regions of the genome that have a higher concentration of CpG sites, known as CpG island

CpG island

In genetics, CpG islands or CG islands are genomic regions that contain a high frequency of CpG sites but to date objective definitions for CpG islands are limited. In mammalian genomes, CpG islands are typically 300-3,000 base pairs in length. They are in and near approximately 40% of promoters of...

s. Many genes in mammalian genomes have CpG islands associated with the start of the gene. Because of this, the presence of a CpG island is used to help in the prediction and annotation of genes.

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 gene

Tumor suppressor gene

A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...

s). In contrast, the hypomethylation of CpG sites has been associated with the over-expression of oncogenes within cancer cells.