Disease relevance of AIDS-097589

• Clusters of CpG dinucleotides implicated by nuclease hypersensitivity as control elements of housekeeping genes [1].
• These findings, besides increasing the proportion of caucasian individuals whose haemophilia B carrier state can be diagnosed from 79% to 89%, demonstrate this widely applicable use of PCR for the detection of DNA polymorphism at cytosine phosphoguanadine dinucleotides irrespective of the methylation status [2].
• These similarities, the presence of inverted repeats often ending with the dinucleotides U-G and C-A, and flanking imperfect direct repeats suggest that viroids may have originated from transposable elements or retroviral proviruses by deletion of interior portions of the viral (or element) DNA [3].
• Despite comparable levels of unmethylated CpG dinucleotides, DNA from serotype 12 adenovirus is immune-stimulatory, but serotype 2 is nonstimulatory and can even inhibit activation by bacterial DNA [4].
• Constitutively methylated CpG dinucleotides as mutation hot spots in the retinoblastoma gene (RB1) [5].

Psychiatry related information on AIDS-097589

• Mutations of the methylated DNA binding protein MeCP2, a multifunctional protein that is thought to transmit epigenetic information encoded as methylated CpG dinucleotides to the transcriptional machinery, give rise to the debilitating neurodevelopmental disease Rett syndrome (RTT) [6].

High impact information on AIDS-097589

• This methylation is present in male gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates [7].
• An unusual sequence arrangement of two AG dinucleotides and an intervening polypyrimidine (Py)-tract at the 3' end of intron 2 is important for Sxl autoregulation [8].
• MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13) [9].
• First, methylation of 5'-CpG-3' dinucleotides within promoters represses transcription, often to undetectable levels [10].
• CpG islands are short stretches of DNA containing a high density of non-methylated CpG dinucleotides, predominantly associated with coding regions [11].

Chemical compound and disease context of AIDS-097589

• Bisulfite genomic sequencing showed significant (>90%) demethylation of CpG dinucleotides spanning MT-I promoter in the hepatoma following treatment with 5-AzaC [12].
• DNA is a target for ultraviolet-B-induced inhibition of contact hypersensitivity, and small DNA fragments such as thymidine dinucleotides (pTpT) can simulate several ultraviolet-induced effects [13].
• Dehydration of 18 with DCC led to the formation of the bicyclic trisanhydride intermediate 19a, which upon reaction with 2',3'-O-isopropylidenetiazofurin (20) or -benzamide riboside (21) followed by hydrolysis and deprotection afforded the desired methylene-bridged dinucleotides 8 and 12, respectively [14].
• The three bacterial products with the greatest potential to function as mucosal adjuvants are the ADP-ribosylating enterotoxins (cholera toxin and the heat-labile enterotoxin of Escherichia coli), synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN), and monophosphoryl lipid A (MPL) [15].
• We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity response to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm2), or topically applied cis-UCA (150 nmol/cm2) or thymidine dinucleotides (pTpT) (5 nmol/cm2) [16].

Biological context of AIDS-097589

• The template must consist of RNA and not DNA sequence, and the terminal unpaired dinucleotides of the RNA are necessary for replication [17].
• The 10.5-base-pair (bp) periodicity of some dinucleotides first found in eukaryotic DNA sequences was interpreted as the expression of curvature of periodic segments of double-stranded DNA, the curvature resulting from co-orientation of periodically spaced 'wedges' between stacked base pairs [18].
• This suggests that methylation in other C-G dinucleotides than those detectable with restriction enzymes can be crucial for gene expression [19].
• Methylated cytosines occur exclusively at CpG dinucleotides, which, although markedly underrepresented in human DNA, are sites for more than 30 percent of all known disease-related point mutations [20].
• Methylation patterns in genomic DNA are readily detectable; for example, 17 CpG dinucleotides in the 5' region of human X-linked PGK-1 (phosphoglycerate kinase 1) were found to be methylated on an inactive human X chromosome, but unmethylated on an active X chromosome [21].

Anatomical context of AIDS-097589

• We report here that bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides induce murine B cells to proliferate and secrete immunoglobulin in vitro and in vivo [22].
• The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC) [23].
• Mutations of CpG dinucleotides located in the triiodothyronine (T3)-binding domain of the thyroid hormone receptor (TR) beta gene that appears to be devoid of natural mutations may not be detected because they are unlikely to produce the clinical phenotype of resistance to thyroid hormone [24].
• Pattern recognition receptors of the innate immune system are able to distinguish certain prokaryotic DNAs from vertebrate DNAs by detecting unmethylated CpG dinucleotides in particular base contexts ('CpG motifs') [25].
• The 5' region of the gene encoding human X chromosome-linked phosphoglycerate kinase 1 (PGK1) is a promoter-containing CpG island known to be methylated at 119 of 121 CpG dinucleotides in a 450-base-pair region on the inactive human X chromosome in the hamster-human cell line X8-6T2 [26].

Associations of AIDS-097589 with other chemical compounds

• Nucleotide-sequence analysis of ADAR2 genomic DNA revealed the presence of adenosine-adenosine (AA) and adenosine-guanosine (AG) dinucleotides at these proximal and distal alternative 3' acceptor sites, respectively [27].
• Cytosine methylation within CpG dinucleotides has been implicated in the regulation of gene expression in vertebrates and, in some cases, has been shown to be causative in repression of transcription [28].
• Other activities suggested for SGP-2 are lipid transport and cell-cell interactions, which are consistent with sequence data that predict binding of dinucleotides, heparin and lipids [29].
• These findings, along with the absence of clustered CpG dinucleotides within the Factor IX locus, suggest that functional differences in DNA methylation related to X chromosome dosage compensation may be limited to CpG clusters [30].
• This latter difference is mainly a consequence of the presence of 5-methylcytosine (m5C) in CpG dinucleotides on the inactive X chromosome [31].

Gene context of AIDS-097589

• DNA sequences of the X-chromosome-linked hypoxanthine phosphoribosyltransferase (HPRT) and glucose 6-phosphate dehydrogenase (G6PD) genes have revealed the presence of clusters of CpG dinucleotides, raising the possibility that such clusters are involved in the control of expression of these genes, which are expressed in all tissues [1].
• The early B cell-specific mb-1 promoter was hypermethylated at CpG dinucleotides in hematopoietic stem cells but became progressively unmethylated as B cell development proceeded [32].
• Immunomers containing RpG dinucleotides showed activity in transfected-HEK293 cells stably expressing mouse TLR9, suggesting direct involvement of TLR9 in the recognition of RpG motif [33].
• Particularly striking is the distribution of CpG dinucleotides within human and rodent APRT genes [34].
• Bacterial DNA and synthetic oligomers containing CpG dinucleotides activate the immune system through Toll-like receptor (TLR) 9 [35].

Analytical, diagnostic and therapeutic context of AIDS-097589

• Circular dichroism of adenosine dinucleotides [36].
• Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides [37].
• A comparison of the frequencies of inferred deamination mutations at CpG and GpC dinucleotides in the two classes of promoters using SNPs in human-chimpanzee sequence alignments shows that CpGs mutate at a lower frequency in the HCG promoters, suggesting that CpGs in the HCG class are hypomethylated in the germ line [38].
• Southern blotting following digestion with the methylation sensitive restriction endonucleases SmaI, HpaII and HhaI, indicated that CpG dinucleotides within the CpG island were unmethylated on the active X chromosome and extensively methylated on the inactive X chromosome [39].
• Pyridine dinucleotides and adenine nucleotides were determined by high-performance liquid chromatography [40].

References