CpG dinucleotide

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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 .


Schematic representation of a CpG dinucleotide as a section of a double-stranded DNA molecule (dsDNA). The actual CpG dinucleotide (5'-deoxycytidine-phosphoric acid-deoxyguanosine-3 ') on the indicated strand (“Watson”) is shown in black. The base pairing to the complementary strand ("crick") is shown in gray. The alignment (5'-3 '), numbering and transitions to parts not shown (wavy lines) of the dsDNA molecule are also shown in gray. The blue marking of the named parts (cytosine-phosphate-guanine) results in the writing "CpG".

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 .

Therapeutic uses

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.

Gene therapy

In bacterial plasmids for gene therapy , the CpG dinucleotides are partially removed in order to avoid premature degradation of the plasmid.

Individual evidence

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