The roles of histone modifications in retinal degeneration
| Project/Area Number |
18K16949
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Iwagawa Toshiro 東京大学, 医科学研究所, 特任研究員 (30638648)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ヒストン修飾 / 網膜変性 / Ezh2 / H3K27me3 / ヒストンメチル化 / Retinal degeneration / Histone methylation / Epigenetics |
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| Outline of Final Research Achievements |
Retinal dystrophy is thought to be caused not only by a gene mutation but by a dysregulated gene expression through an epigenetic mechanism, including a histone modification. To clarify the contribution of H3K27me3, a repressive histone modification, to retinal dystrophy, MNU, which causes photoreceptor degeneration, was administered to a control and a conditional knockout of Ezh2 (Ezh2-cKO), a methyltransferase for H3K27me3, mouse and retinas were analyzed by immunohistochemistry and RT-qPCR. Compared with the control, the Ezh2-cKO retina showed milder photoreceptor degeneration, especially in male mice, and the expression of a gene related to necroptosis, a programmed form of necrosis, was lower in the Ezh2-cKO retina. The results suggest the contribution of H3K27me3 to necroptosis of photoreceptor cells during retinal degeneration.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒストン修飾を含むエピジェネティックな発現制御機構と様々な疾患との関連は明らかにされつつあるが、網膜変性に対する寄与はよく分かっておらず、役割が比較的よく分かっているH3K27me3の網膜変性における知見も非常に少ない。本研究によりH3K27me3が視細胞の変性の進行に寄与していることが示唆され、さらに変性を促進する薬剤であるMNUに対する反応性の性別差から、細胞死の中でもネクロトーシスに関与する可能性が考えられる。今後視細胞変性に対して促進性あるいは抑制性に働く因子との関係からそのメカニズムが明らかとなり、変性を抑える手立ての一助となることが期待される。
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Report
(3 results)
Research Products
(1 results)
