| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
SWI/SNF chromatin remodeling factor was frequently inactivated in various types of cancers by somatic mutations of its components. However, the mechanism how SWI/SNF inactivation is involved in carcinogenesis is not well understood. In this study, we aimed to clarify molecular mechanism by focusing on the production of gene expression heterogeneity (diversity). First, SWI/SNF inactivated cell line was established by double knockout of SWI/SNF components, SMARCA2 and SMARCA4, using CRISPR/Cas9 system (DKO cell line). Then, diversity of gene expression status, namely diversity of nucleosome positioning, was analyzed by NOMe-seq. It was revealed that the diversity of nucleosome positioning was increased in DKO cell line compared to SWI/SNF wild type cell line. This result suggested that gene expression heterogeneity was produced by SWI/SNF inactivation, and this might be involved in carcinogenesis.
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