2017 Fiscal Year Final Research Report
Investigation of the transcriptional coregulator involved in crosstalk between histone acetylation and methylation
| Project/Area Number |
16K15216
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 転写コレギュレーター / ヒストン修飾 / 細胞周期 |
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| Outline of Final Research Achievements |
Nardilysin (NRDC) is a metalloendopeptidase of the M16 family and activates ectodomain cleavage of membrane proteins on the cell surface. On the other hand, nuclear NRDC specifically binds to H3K4me2 and controls transcriptional regulation. Analysis of genetically-modified mice revealed that NRDC play important roles in cancer, inflammation and energy metabolism. In the present study, we combined high-throughput chromatin immunoprecipitation-sequencing and RNA-sequencing analyses to achieve the first genome-wide identification of NRDC target genes in immortalized mouse embryo fibroblasts. We found that global H3K9ac and H3K4me2 levels at NRDC-binding promoters were controled and that a set of genes integral to cell cycle maintenance was directly activated by NRDC. Collectively, these results suggest that the NRDC-mediated epigenetic regulation of cell cycle-associated genes is a fundamental component of the biological functions of NRDC.
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| Free Research Field |
薬理学、分子病態医化学
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