| Project/Area Number |
19K24152
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0907:Oral science and related fields
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 骨格筋 / 転写コファクター / サルコペニア / myogenesis / Sarcopenia / Transcription / Epigenetics / Muscle / Zfp423 |
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| Outline of Research at the Start |
We hypothesize that Zfp423 is an important network center to integrate multiple signaling pathways at the transcriptional level via recruitment of chromatin remodeling complexes. Our questions are: 1) How does Zfp423 affect satellite cell function? and 2) What role does Zfp423 have in sarcopenia?
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| Outline of Final Research Achievements |
In order to identify Zfp423 targets we performed ChIP-Seq using anti-FLAG antibody in C2C12 cells stably expressing FLAG-Zfp423. A total of 749 Zfp423 bound regions were identified. Approximately 65% of peaks were found at promoters. Another 15% of peaks were within intronic regions. Motif discovery at Zfp423 peaks produced two unique motifs enriched at a majority of Zfp423 peaks. Gene ontology analysis of Zfp423-associated genes revealed significant association to functions involving nucleic acid binding, signal transduction, transporter activity, proliferation and development. These findings provide additional new evidence of a role of Zfp423 in muscle cell function. We demonstrate that Zfp423 binds to proximal regulatory elements of target genes and mediates transcription-level events. Further functional characterization of Zfp423 will improve our understanding of the molecular mechanisms regulating muscle homeostasis.
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| Academic Significance and Societal Importance of the Research Achievements |
加齢に伴う骨格筋の量と機能の低下はサルコペニアと呼ばれ，高齢化が加速している先進国が直面している主要な健康問題となっています．さらにサルコペニアは，死亡率，種々の疾患，QOLに重大な影響を及ぼし，医療費を圧迫している原因となっています．今回の研究からサテライト細胞による骨格筋再生を担うZfp423の遺伝子発現制御メカニズムの一端を明らかにすることができました．現在のところ，サルコペニアを予防・治療する薬剤は存在しません．よって，今後の研究を発展させることにより筋再生を促す手法を確立することができれば，大いに高齢社会の先進国の人々の健康に貢献することが期待されます．
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