Chromosomal Losses are Associated with Hypomethylation of the Gene-Control Regions in the Stomach with a Low Number of Active Genes

Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Journal of Korean Medical Science (Impact Factor: 1.25). 01/2009; 23(6):1068-89. DOI: 10.3346/jkms.2008.23.6.1068
Source: PubMed

ABSTRACT Transitional-CpG methylation between unmethylated promoters and nearby methylated retroelements plays a role in the establishment of tissue-specific transcription. This study examined whether chromosomal losses reducing the active genes in cancers can change transitional-CpG methylation and the transcription activity in a cancer-type-dependent manner. The transitional-CpG sites at the CpG-island margins of nine genes and the non-island-CpG sites round the transcription start sites of six genes lacking CpG islands were examined by methylation-specific polymerase chain reaction (PCR) analysis. The number of active genes in normal and cancerous tissues of the stomach, colon, breast, and nasopharynx were analyzed using the public data in silico. The CpG-island margins and non-island CpG sites tended to be hypermethylated and hypomethylated in all cancer types, respectively. The CpG-island margins were hypermethylated and a low number of genes were active in the normal stomach compared with other normal tissues. In gastric cancers, the CpG-island margins and non-island-CpG sites were hypomethylated in association with high-level chromosomal losses, and the number of active genes increased. Colon, breast, and nasopharyngeal cancers showed no significant association between the chromosomal losses and methylation changes. These findings suggest that chromosomal losses in gastric cancers are associated with the hypomethylation of the gene-control regions and the increased number of active genes.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: The methylation-variable sites around CpG islands are frequently overmethylated in Helicobacter pylori-infected stomachs. Age-related patterns of the overmethylation changes were compared between the fast-growing antrum cells and the slow-growing body cells. Materials & methods: A total of 316 H. pylori-positive tissues and 380 H. pylori-negative tissues were obtained by endoscopic biopsy. The methylation-variable sites of ten housekeeping genes and nine tissue-specific genes were semiquantitatively analyzed, based on the ten-level classification of methylation-specific PCR intensity. The overmethylated genes were scored when their methylation levels were higher than an intermediate level of each gene common in the H. pylori-negative mucosa. Results: The age-dependent methylation level of the inactive APC gene observed similarly in the antrum and the body was used as an age standard of methylation variation in a biopsy tissue. The overmethylation of housekeeping genes and stomach-specific genes rapidly increased to a high plateau frequency in the young-aged APC methylation cases (mean age: 43 years) in the H. pylori-positive antrum. In the H. pylori-positive body, most of the overmethylated housekeeping genes slowly increased to a peak frequency in the middle-aged APC methylation cases (mean age: 53 years). The housekeeping gene pairs showed high correlations (Spearman's correlation coefficient > 0.4) in both the antrum and the body. Conclusion: The overmethylation of housekeeping genes rapidly and slowly increased to a high frequency in concordance with a rapid and slow growth of epithelial cells in the H. pylori-infected stomach.
    Epigenomics 06/2013; 5(3):283-99. DOI:10.2217/epi.13.17 · 5.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A chronic inflammatory condition of gastric mucosa can facilitate the influx of new stem cells into the stomach. Epigenetic codes, such as DNA methylation, may be responsible for the stable maintenance of epigenetic phenotypes established in the new stomach-adapted stem cells. A number of hypotheses have been made for the role of CpG-island methylation, which is common in the Helicobacter pylori-infected stomach. However, they could not explain the plausible role of CpG-island methylation in the re-establishment of epigenetic phenotypes. These islands are highly repetitive sequences densely methylated throughout the human genome, the so-called parasitic retroelements, which expand a number of cDNA copies with reverse transcriptase. The densely methylated retroelements adjacent to the host genes can form the transitional-CpG sites around gene-control regions that are barely methylated. This review focuses on the putative role of transitional CpG methylation in the adaptive differentiation of new stem cells in the H. pylori-infected stomach.
    Epigenomics 10/2012; 4(5):527-35. DOI:10.2217/epi.12.51 · 5.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The CYP21 (steroid 21-hydroxylase) gene is involved in the synthesis of steroid hormones. Bov-A2 is a retroposon that is common in ruminant genomes. The promoter region of bovine CYP21 contains a short interspersed nucleotide element of Bov-A2, which overlaps a putative Sp1 binding site. We looked for RFLP/HpaII polymorphism in the Bov-A2 element in bovine Zebu breeds by PCR-RFLP, and examined whether polymorphism in this element is associated with methylation. Among DNA samples from 135 Brazilian Zebu breed cattle, we identified an RFLP/HpaII polymorphism (T/C), which, based on a restriction methylation-sensitive assay employing HpaII and isoschizomer MspI enzymes (methylation-sensitive and -non-sensitive enzymes, respectively), appears to be a DNA methylation point. This is the first report of this polymorphism and on DNA methylation in the bovine CYP21 promoter region in Brazilian Zebu cattle.
    Genetics and molecular research: GMR 01/2011; 10(3):1409-15. DOI:10.4238/vol10-3gmr1266 · 0.85 Impact Factor

Full-text (3 Sources)

Available from
Apr 10, 2015