| Project/Area Number |
18K06061
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 43010:Molecular biology-related
|
|---|
| Research Institution | Hokkaido University (2020)
Kochi University (2018-2019) |
|---|
Principal Investigator |
Ohta Shinya 北海道大学, 遺伝子病制御研究所, 准教授 (00631194)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 染色体 / セントロメア / ヘテロクロマチン / クロマチン |
|---|
| Outline of Final Research Achievements |
Centromere/kinetochore is essential for proper segregation of the genome during mitosis. It has been indicated that precise heterochromatization at pricentromeric alpha-satellites is required for maintenance of centromere function. Currently our proteomics has indicated chromosomal association of uncharacterized protein, ZNF518. Therefore we verified this hypothesis observing localization of GFP fusion and found its pericentromere localization with satellite DNA binding protein CENP-B dependent manner. Also GFP localization trucking with various truncated ZNF518 shows two essential domains for the pericentromere localization. A fluorescence microscopy-based interaction-trap assay on human chromosomes suggests these two domains are independent CENP-B or HP1 interacting domains. Since G9a histone metyltransferase interaction of ZNF518 has been reported, we suppose that ZNF518 protein is involved in CENP-B dependent pericentromeric heterochromatization.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は、ペリセントロメア領域のヘテロクロマチン化に関して、新しい分子機構のモデルがを提唱するものである。セントロメアがその機能を維持する機構については不明な点が多く、本成果は、どのように世代間で染色体が維持され伝播するのか、その機構の全容を解明の一端を担うことができた点において意義があり、その機構は細胞の癌化などの疾患への機序と密接に関わっている。今後は、セントロメアや染色体全体の安定性とその破綻によって引き起こされる疾患の本質的な理解へ貢献を目指す。
|
