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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Methylation patterns of the human beta-glucuronidase gene locus: boundaries of methylation and general implications for frequent point mutations at CpG dinucleotides.

Methylation of CpG islands spanning promoter regions is associated with control of gene expression, although it is unclear what mechanisms define the boundaries between methylated and unmethylated regions in the genome. Methylation of genomic DNA in mammals also affects the frequency of inherited diseases by predisposing them to CpG mutations. To gain insight into these issues, we investigated patterns of cytosine methylation on almost the entire beta-glucuronidase gene (GUSB) from normal leukocyte DNAs by bisulfite genomic sequencing. We mapped the boundaries of methylation that flank the 5'- and 3'-ends of the CpG island region, and correlated methylation status with transitional mutations at CpG sites. GenBank sequence analyses showed that the CpG island of human GUSB is juxtaposed with multiple Alu repeats and also includes multiple Sp1 sites upstream and downstream of the transcription start, which has been suggested to prevent CpG islands from becoming methylated. We show that cytosine methylation is extensive across the entire gene except for CpG sites in the proximal promoter region, exon 1, and part of intron 1; the unmethylated CpG island is embedded between densely methylated flanking regions containing multiple Alu repeats; a sharp boundary separates the methylated and unmethylated regions of the 5'-flank of the CpG island, but a gradual change in methylation density over 1.0 kb is observed in the 3'-flank of the CpG island; boundaries of the 5'-end and 3'-end of the CpG island contain multiple Sp1 sites in addition to Alu repeats; methylation in both strands is symmetrical except at the boundary regions between methylated and unmethylated regions; and nonmethylation of exon 1 correlates with the absence of transitional mutations at CpG sites in exon 1.[1]

References

  1. Methylation patterns of the human beta-glucuronidase gene locus: boundaries of methylation and general implications for frequent point mutations at CpG dinucleotides. Tomatsu, S., Orii, K.O., Islam, M.R., Shah, G.N., Grubb, J.H., Sukegawa, K., Suzuki, Y., Orii, T., Kondo, N., Sly, W.S. Genomics (2002) [Pubmed]
 
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