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Chemical Compound Review:

AC1LA626 [3-[[5-(2-amino-6-oxo-3H- purin-9-yl)-3...

Synonyms: 5'-CG-3'

Munnes, M. et al., Behn-Krappa, A. et al., Kochanek, S. et al., Kochanek, S. et al., Zeschnigk, M. et al., et al.

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Disease relevance of 5'-CG-3'

In normal B lymphocytes, in two cases of chronic lymphatic B-cell leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences in this gene segment are devoid of methylation [1].
DNA elements have been specifically in vitro methylated by the HpaII (5'-CCGG-3'), the FnuDII (5'-CGCG-3'), or the CpG DNA methyltransferase from Spiroplasma species (M-SssI; 5'-CG-3') [2].
We have also demonstrated by the in vitro premethylation of a RET promoter-chloramphenicol acetyltransferase (CAT) gene construct and transient transfection experiments into neuroblastoma cells that the transcriptional activity of the RET promoter is decreased by HpaII (5'-CCGG-3') methylation and abolished by SssI (5'-CG-3') methylation [3].
A fully 5'-CG-3' but not a 5'-CCGG-3' methylated late frog virus 3 promoter retains activity [4].
Several lines of evidence demonstrate that the DNA of the iridovirus frog virus 3 (FV3) is methylated in all 5'-CG-3' sequences both in virion DNA and in the intracellular viral DNA at late times after infection [4].

High impact information on 5'-CG-3'

High levels of 5'-CG-3' methylation in Alu elements could contribute to their general transcriptional inactivity [5].
(iv) The results of cell-free transcription experiments with Alu elements suggest that the in vitro transcription of Alu elements can be inhibited by 5'-CG-3' methylation [5].
This finding is not consistent with the notion that hypermethylation would be a sufficient condition in itself for 5'-CG-3' sequences to undergo loss of 5-methyl-deoxycytidine (5-mC) due to deamination and subsequent mutation [5].
The DNA from the human HeLa cell line is highly methylated at all 5'-CG-3' sequences in the TNF-alpha and -beta genes [1].
In human T and B lymphocytes, the main producers of TNF-beta, in three instances of chronic lymphatic leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences are unmethylated in this region [1].

Biological context of 5'-CG-3'

We have investigated the promoter and exon 1 region, the nucleotide -300 to +300 region of this gene relative to the position of transcriptional initiation at nucleotide +1, particularly with respect to the extent of DNA methylation at the 5'-CG-3' sequences and its changes upon induction [6].
At the other five 5'-CG-3' dinucleotides, differential methylation is less pronounced, i.e. 45-70% on the maternal chromosome and 5-14% on the paternal chromosome [7].
The data presented are remarkable in that a highly 5'-CG-3'-enriched segment of the human genome with 49 5'-CG-3' dinucleotide pairs in 400 bp within the putative promoter region is completely devoid of 5-mC residues, although this control region is not actively transcribed in most adult human tissues [3].
One of the cellular DNA sequences abutting the right Ad12 DNA terminus in cell line T637 (os2) is represented only once in the hamster genome and has a strikingly low abundance of 5'-CG-3' dinucleotide sequences [8].
The 5' region of this presumptive viral gene is also methylated in all 5'-CG-3' positions [9].

Anatomical context of 5'-CG-3'

In cell line HE2, the same promoter is permanently shut off and all 5'-CG-3' sequences are methylated in both strands [10].
We have shown previously that 30-mer oligonucleotides containing hexamer palindromic sequences with 5'-CG-3' motif(s) induce interferon (IFN), activate natural killer (NK) cells, and thus exhibit tumor-regressing activity [11].

Associations of 5'-CG-3' with other chemical compounds

The region of the IL-2R alpha gene analyzed for 5'-CG-3' methylation by the genomic sequencing method or a polymerase chain reaction-based method subsequent to HpaII or HhaI cleavage of the DNA does not seem to be significantly methylated in most cell types tested, except for the cytidine residue in position +198 which is partly methylated [6].
The preferential binding of hedamycin to 5'-CG-3' over 5'-TG-3' binding sites is explained in terms of the orientation and location of the N,N-dimethylvancosamine saccharide in the minor groove [12].
These results predict that the more favorable DNA sequence for interstrand crosslinking is 5'-GC-3' rather than the previously proposed 5'-CG-3' and that thymine methyl groups adjacent to guanine will inhibit interstrand crosslinking [13].

Gene context of 5'-CG-3'

All 5'-CG-3' sites studied in the TNF-alpha and -beta genes are methylated in DNA from human sperm [14].
Hence, the genes for B3, P4.2, and beta-spectrin (beta-SP) appear to be suitable models to study the relationship between methylation of promoter 5'-CG-3' sites and the sequential expression of genes during human erythroid development and differentiation [15].
In cell lines HE1 and uc2, the late E2A promoter is active and all thirteen 5'-CG-3' sequences between positions +24 and -160 are unmethylated [10].
However, > 96% of all of the 23 5'-CG-3' dinucleotides around SNRPN exon 1 are methylated on the maternal chromosome and completely devoid of methylation on the paternal chromosome [7].
Moreover, methylation of 5'-CCTGG-3' pentanucleotides was not detected within the closely related Myf-4 gene, which is normally 5'-CG-3' hypermethylated [16].

References

DNA methylation profiles in the human genes for tumor necrosis factors alpha and beta in subpopulations of leukocytes and in leukemias. Kochanek, S., Radbruch, A., Tesch, H., Renz, D., Doerfler, W. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
The topology of the promoter of RNA polymerase II- and III-transcribed genes is modified by the methylation of 5'-CG-3' dinucleotides. Muiznieks, I., Doerfler, W. Nucleic Acids Res. (1994) [Pubmed]
A 5'-CG-3'-rich region in the promoter of the transcriptionally frequently silenced RET protooncogene lacks methylated cytidine residues. Munnes, M., Patrone, G., Schmitz, B., Romeo, G., Doerfler, W. Oncogene (1998) [Pubmed]
A fully 5'-CG-3' but not a 5'-CCGG-3' methylated late frog virus 3 promoter retains activity. Munnes, M., Schetter, C., Hölker, I., Doerfler, W. J. Virol. (1995) [Pubmed]
DNA methylation in the Alu sequences of diploid and haploid primary human cells. Kochanek, S., Renz, D., Doerfler, W. EMBO J. (1993) [Pubmed]
The state of DNA methylation in the promoter and exon 1 regions of the human gene for the interleukin-2 receptor alpha chain (IL-2R alpha) in various cell types. Behn-Krappa, A., Doerfler, W. Hum. Mol. Genet. (1993) [Pubmed]
Imprinted segments in the human genome: different DNA methylation patterns in the Prader-Willi/Angelman syndrome region as determined by the genomic sequencing method. Zeschnigk, M., Schmitz, B., Dittrich, B., Buiting, K., Horsthemke, B., Doerfler, W. Hum. Mol. Genet. (1997) [Pubmed]
The structure of adenovirus type 12 DNA integration sites in the hamster cell genome. Knoblauch, M., Schröer, J., Schmitz, B., Doerfler, W. J. Virol. (1996) [Pubmed]
Patterns of frog virus 3 DNA methylation and DNA methyltransferase activity in nuclei of infected cells. Schetter, C., Grünemann, B., Hölker, I., Doerfler, W. J. Virol. (1993) [Pubmed]
Genomic sequencing reveals a 5-methylcytosine-free domain in active promoters and the spreading of preimposed methylation patterns. Toth, M., Lichtenberg, U., Doerfler, W. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
Hexamer palindromic oligonucleotides with 5'-CG-3' motif(s) induce production of interferon. Sonehara, K., Saito, H., Kuramoto, E., Yamamoto, S., Yamamoto, T., Tokunaga, T. J. Interferon Cytokine Res. (1996) [Pubmed]
Structural investigation of the hedamycin:d(ACCGGT)2 complex by NMR and restrained molecular dynamics. Owen, E.A., Burley, G.A., Carver, J.A., Wickham, G., Keniry, M.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
Identification of local determinants of DNA interstrand crosslink formation by cyclophosphamide metabolites. Hausheer, F.H., Singh, U.C., Saxe, J.D., Colvin, O.M. Anticancer Drug Des. (1989) [Pubmed]
Interindividual concordance of methylation profiles in human genes for tumor necrosis factors alpha and beta. Kochanek, S., Toth, M., Dehmel, A., Renz, D., Doerfler, W. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
Relationships between DNA methylation and expression in erythrocyte membrane protein (band 3, protein 4.2, and beta-spectrin) genes during human erythroid development and differentiation. Remus, R., Kanzaki, A., Yawata, A., Wada, H., Nakanishi, H., Sugihara, T., Zeschnigk, M., Zuther, I., Schmitz, B., Naumann, F., Doerfler, W., Yawata, Y. Int. J. Hematol. (2005) [Pubmed]
Evidence that cytosine residues within 5'-CCTGG-3' pentanucleotides can be methylated in human DNA independently of the methylating system that modifies 5'-CG-3' dinucleotides. Franchina, M., Kay, P.H. DNA Cell Biol. (2000) [Pubmed]

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