| Budget Amount *help |
¥48,360,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥11,160,000)
Fiscal Year 2013: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2012: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2011: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
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| Research Abstract |
In tis study, we tried to identify factors that determine DNA methylation patterns of human cells, with a long-term goal of clarifying mechanisms regulating gene expression. First, we identified ZBTB24 protein as a novel methylation pattern determinant, based on the study of an immune-deficiency syndrome accompanied by DNA hypomethylation at certain DNA sequences. A gene knockout study in mice confirmed that it is indeed a factor regulating DNA methylation. Second, based on the comparative study of methylation patterns between human and chimpanzee, we identified CTCF protein, a transcription factor, and its target sequence as methylation determinants. Species-specific sequence changes that disrupted CTCF binding were correlated with hypermethylation. Lastly, we identified CpG dinucleotide density in tandem repetitive sequences as another determinant. Our results provide a basis to study the roles of methylation in evolution, variability and disease such as cancer.
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