Disease relevance of F8a

• The tumour suppressor gene RASSF1A is frequently silenced in lung cancer and other sporadic tumours as a result of hypermethylation of a CpG island in its promoter [1].
• CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression [2].
• Here we show that our RSV-derived reporter proviruses linked to the mouse aprt gene CpG island remain undermethylated and keep their transcriptional activity after stable transfection into both avian and nonpermissive mammalian cells [2].
• A novel homeodomain-encoding gene is associated with a large CpG island interrupted by the myotonic dystrophy unstable (CTG)n repeat [3].
• In this study, we show that low levels of CpG island methylation occur in the normal intestinal mucosa of Apc(Min/+) mice and are increased in Multiple Intestinal Metaplasia (Min) polyps [4].

Psychiatry related information on F8a

• The syndrome results from the absence of expression of the FMR1 gene (fragile mental retardation 1) owing to the expansion of a CGG trinucleotide repeat located in the 5' untranslated region of the gene and the subsequent methylation of its CpG island [5].

High impact information on F8a

• Gene silencing through de novo methylation of CpG island promoters contributes to cancer [6].
• Here we show that in the affected individual, in a transgenic model and in differentiating embryonic stem cells, transcription of antisense RNA mediates silencing and methylation of the associated CpG island [7].
• We suggest that mutation-like gene inactivation due to CpG island methylation is widespread in many cell lines and could explain the loss of cell type-specific functions in culture [8].
• Imprinted expression of the Igf2r gene depends on an intronic CpG island [9].
• Transfection experiments in vitro show that the demethylation is rapid, is specific for embryonic cell-types and affects a variety of different CpG island sequences [10].

Chemical compound and disease context of F8a

• The methylation status of the CpG island located within the ribosomal RNA (rRNA) promoter in human hepatocellular carcinomas and pair-matched liver tissues was analyzed by bisulfite genomic sequencing [11].

Biological context of F8a

• The utrophin promoter is associated with a CpG island at the 5'-end of the gene, and sequence analysis of the 5'-UTR reveals several Sp1 binding sites and the absence of TATA or CAAT motifs [12].
• This housekeeping gene has a CpG island that extends over the gene promoter and includes the first two exons [13].
• In particular, a CpG island that comprises one of the two strong promoters is unmethylated at both parental alleles, and DNase I hypersensitive sites in and around the strong promoters are consistently present on both parental chromosomes [14].
• Deletion or mutagenesis of the Sp1 sites causes de novo methylation of the CpG island in a transgenic mouse assay [13].
• These findings reveal a previously unknown effect of IL-1beta and NO on gene expression, and demonstrate a novel pathway for gene silencing based on activation of DNA MeTase by NO and acute modification of CpG island methylation [15].

Anatomical context of F8a

• Hypermethylation of a CpG island in the noncoding exon 1 was associated with silencing of this gene in malignant B cells [16].
• It was found that HpaII site H-7 in the CpG island of the X-chromosome-linked Pgk-1 gene is less than or equal to 10% methylated in oocytes and male embryos but becomes 40% methylated in female embryos at 6.5 days; about the time of X-chromosome inactivation of the inner cell mass [17].
• We have found that this CpG island includes a novel intronic promoter that is active in embryonic and germ cells [18].
• In the mouse preimplantation embryo, most genes are unmethylated but a wave of de novo methylation prior to gastrulation generates a bimodal pattern characterized by unmethylated CpG island-containing housekeeping genes and fully modified tissue-specific genes [19].
• The CpG island-like pVHCk plasmid containing the bacterial chloramphenicol acyltransferase (CAT) gene under the control of SV40 early promoter was transfected in L929 mouse fibroblast cells [20].

Associations of F8a with chemical compounds

• This effect of l-methionine was associated with an increase in the number of methylated cytosines in the CpG island of the reelin promoter region [21].
• Here, we have investigated whether ex vivo preselection of retrovirally transduced stem cells on the basis of expression of the green fluorescent protein driven by the CpG island phosphoglycerate kinase promoter can ensure subsequent long-term expression of a cis-linked beta-globin gene in the erythroid lineage of transplanted mice [22].
• The mouse dihydrofolate reductase (Dhfr) promoter region is buried within a CpG island (a region rich in unmethylated CpG dinucleotides), has a high G+C content, and lacks CAAT and TATA elements [23].
• Isolation of a novel retinoic acid-responsive gene by selection of genomic fragments derived from CpG-island-enriched DNA [24].
• Cytosine methylation patterns in genomic DNA are significantly altered in cancer, and de novo CpG island methylation has been implicated in tumor suppressor gene silencing [25].

Physical interactions of F8a

• The 5'-flanking region lacks both TATA and CCAAT boxes but contains five putative Sp1 binding sites located in a CpG island [26].

Regulatory relationships of F8a

• The mouse CREB gene is expressed from a promoter that is situated in a CpG island [27].

Other interactions of F8a

• Lambda G28, a mouse genomic clone homologous to the human P3 gene and associated with a CpG island, also hybridizes to human probes for the neighboring GdX gene [28].
• We show that a CpG island associated with Gatm is unmethylated, as is a large CpG island associated with a neighboring gene [29].
• These findings show a link between inactivation of the pRb pathway and induction of DNA hypermethylation of CpG island-containing genes in tumorigenesis [30].
• Here we describe a novel gene, Enox (expressed neighbor of Xist), that maps to an unmethylated CpG island 10 kb upstream of Xist [31].
• Because there is a 283-bp CpG island region in the HO-1 promoter, we hypothesized that methylation of the island is responsible for the age-related HO-1 down-regulation in the cortex [32].

Analytical, diagnostic and therapeutic context of F8a

• Gene silencing by CpG island promoter hypermethylation has awakened the interest for DNA demethylating agents as chemotherapy drugs [33].
• In this method, referred to as CpG-selected and amplified binding, fragments derived from the CpG island fraction of the murine genome are selected by a gel mobility shift assay using in vitro-transcribed and -translated RXR-RAR [24].
• Methylation status was assessed using regular and quantitative methylation-specific PCR and the CpG island was found to be hypomethylated at all ages [32].
• Using pulsed field gel electrophoresis and Southern hybridization, we determined the approximate location of each probe with respect to the CpG island in both the DM and the chromosome [34].
• Analysis of the 5' upstream region by DNA sequencing and Southern blotting suggested that it contained a CpG island, and a major site of transcription initiation 201 bp upstream of the translation start site was found by RNase protection and primer extension [35].

References