| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
Histone modification is related to malignant features of neoplastic cells. We found that the knockdown of a histone demethylase KDM4C eliminated colonosphere formation.β-catenin upregulated KDM4C expression in colonospheres. Microarray analysis identified the JAG1 gene that codes for a notch ligand Jagged1 responsible for sphere formation as a target of KDM4C. KDM4C knockdown suppressed the expression of JAG1 gene, and the downregulation recapitulated the impaired colonosphere formation. JAG1 is also a target of β-catenin, and chromatin immunoprecipitation analysis showed the binding of β-catenin and KDM4C onto the JAG1 promoter during colonosphere formation. KDM4C knockdown inhibited the binding of β-catenin on the JAG1 promoter and blunted JAG1 expression in colonospheres. These data indicate that KDM4C maintains the sphere forming capacity in CRCs by mediating the β-catenin-dependent transcription of JAG1 in a feed-forward manner.
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