A CpG dinucleotide is a chemical combination of two nucleotides that have the nucleobases cytosine and guanine . Occasionally, other names are used, such as CG -stelle , CG-Ort , CpG- Motiv and the like. Ä. In English, CpG site and CpG dinucleotide are common.
In general, the term “CpG dinucleotide” refers to a location within the genetic make-up ( DNA ) that contains deoxycytidine - phosphoric acid - deoxyguanosine (in the 5'-3 ' direction). Due to the complementary base pairing at such a point, which is also called the CpG site , two dinucleotides occur in the DNA double strand at each point.
The CpG sites play a special role in the genomes of some living things (e.g. in mammals) because they are the subject of DNA methylation there and have a special frequency and distribution. The CpG sites or dinucleotides should not be confused with the CpG islands . CpG islands are defined areas where CpG sites are more abundant than other sections of the underlying genome .
Within double-stranded DNA, CpG is a sequence that is exactly the same on the complementary strand in the 5 '- 3' direction:
5' ... pNpNpNpCpGpNpNpN ... 3' | | | | | | | | 3' ... NpNpNpGpCpNpNpNp ... 5'
(N: beliebige Nukleinbase)
The chemical composition of a DNA-internal CpG motif is shown schematically opposite.
Distribution of the CpG motif
Since four nucleobases ( A , C , G and T ) are represented in the DNA, there are 4 * 4 = 16 different two-base sequence motifs (ApA, ApC, ..., CpG, ..., GpC, .. ., TpG, TpT). The CpG motif differs from the other 15 two- base motifs in that it has a different distribution and biological function in the double-stranded DNA of various living things, including humans, than the other two-base motifs. The CpG motif occurs there statistically in CpG islands and can be methylated in different ways. The DNA methylation resulting from cytosine to 5-methylcytosine (guanosine is not methylated). The degree of methylation of CpG sites, especially in the CpG islands, affects gene regulation and other epigenetic properties. The methylation of CpG sites plays a crucial role in cancer research and treatment, as it is often disturbed in tumors.
The low statistical frequency of CG sequences is due to CG suppression .
Methyl CpG binding proteins
Methyl-CpG-binding domain protein 1 ( Mbd1 ) binds to methylated CpG dinucleotides, as does Kaiso , the Kaiso-like proteins and SRA domain proteins .
Adjuvant effect in vaccines
In bacteria , CpG sites often do not have the same distribution, methylation and importance as in humans . These differences in foreign DNA are recognized by the innate immune defense of humans (and that of other vertebrates ) and some immune cells are activated. The intracellular pattern recognition receptor TLR-9 plays the decisive role here . This property of the unmethylated CpG motifs can be exploited to achieve an adjuvant effect in the organism. It can be produced synthetically, nukleasestabile CpG oligonucleotides as adjuvant ( adjuvant ) in clinical studies for the therapy of tumor diseases (including cancer vaccines ), infectious diseases and allergies tested. The stability against nucleases is achieved by a phosphorothioate modification in which an oxygen atom of the phosphate residue is replaced by a sulfur atom.
In bacterial plasmids for gene therapy , the CpG dinucleotides are partially removed in order to avoid premature degradation of the plasmid.
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