| Project/Area Number |
26253075
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TANAKA Sakae 東京大学, 医学部附属病院, 教授 (50282661)
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| Co-Investigator(Kenkyū-buntansha) |
廣瀬 旬 東京大学, 医学部附属病院, 助教 (00456112)
武冨 修治 東京大学, 医学部附属病院, 講師 (70570018)
門野 夕峰 東京大学, 医学部附属病院, 准教授 (70401065)
田中 滋之 東京大学, 医学部附属病院, その他 (10645857)
安井 哲郎 東京大学, 医学部附属病院, 講師 (30583108)
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| Co-Investigator(Renkei-kenkyūsha) |
ABURATANI Hiroyuki 東京大学, 先端科学技術研究センター, 教授 (10202657)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥41,340,000 (Direct Cost: ¥31,800,000、Indirect Cost: ¥9,540,000)
Fiscal Year 2017: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2016: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2015: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2014: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
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| Keywords | 破骨細胞 / エピジェネティクス / 次世代シーケンサー / PU.1 / IRF8 / NFATc1 / 骨代謝学 / シグナル伝達 |
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| Outline of Final Research Achievements |
RANKL induces osteoclast (OC) differentiation from bone marrow-derived macrophages (BMMs). NFATc1 and IRF8 play positive and negative roles, respectively, in this process. We used chromatin immunoprecipitation and formaldehyde-assisted isolation of regulatory elements followed by sequencing to show that PU.1 transcription factor binding motifs were overrepresented at active cis-regulatory regions in both murine BMMs and OCs, while IRF and NFAT binding motifs were selectively enriched at these regions in BMMs and OCs, respectively.
BMM-specific PU.1 binding sites were observed to overlap with IRF8 binding sites in BMMs, and this also occurred for OC-specific PU.1 binding sites and NFATc1 binding sites in OCs. Our results suggest that PU.1 switches its transcription partner from IRF8 to NFATc1, and alters the binding regions during RANKL-induced osteoclastogenesis, which is associated with changes in epigenetic profiles and the control of cell-type specific gene expression.
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