A Comprehensive Analysis of Allelic Methylation Status of CpG Islands on Human Chromosome 21q

• DOI: 10.1101/gr.1351604
• Publication Date: 2004-02-03T02:03:36Z
• Authors: Yoichi Yamada; Hidemi Watanabe; Fumihito Miura; Hidenobu Soejima; Michiko Uchiyama; Tsuyoshi Iwasaka; Tsunehiro Mukai; Yoshiyuki Sakaki; Takashi Ito
• Keywords: Male; 0301 basic medicine; Chromosomes, Human, Pair 21; Mosaicism; Placenta; Chromosome Mapping; Computational Biology; DNA; Sequence Analysis, DNA; DNA Methylation; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Research Design; Leukocytes; Humans; CpG Islands; Female; Alleles

Approximately half of all human genes have CpG islands (CGIs)around their promoter regions. Although CGIs usually escape methylation, those on Chromosome X in females and those in the vicinity of imprinted genes are exceptions: They have both methylated and unmethylated alleles to display a “composite” pattern in methylation analysis. In addition, aberrant methylation of CGIs is known to often occur in cancer cells. Here we developed a simple HpaII-McrBC PCR method for discrimination of full, null, incomplete, and composite methylation patterns, and applied it to all computationally identified CGIs on human Chromosome 21q. This comprehensive analysis revealed that, although most CGIs (103 out of 149)escape methylation, a sizable fraction (31 out of 149)are fully methylated even in normal peripheral blood cells. Furthermore, we identified seven CGIs showing the composite methylation, and demonstrated that three of them are indeed methylated monoallelically. Further analyses using informative pedigrees revealed that two of the three are subject to maternal allele-specific methylation. Intriguingly, the other CGI is methylated in an allele-specific but parental-origin-independent manner. Thus, the cell seems to have a broader repertoire of methylating CGIs than previously thought, and our approach may contribute to uncover novel modes of allelic methylation.