| Project/Area Number |
24591386
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
KIRITO Keita 山梨大学, 総合研究部, 教授 (90306150)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Kei 山梨大学, 医学部附属病院, 医員 (20447709)
MITSUMORI Toru 山梨大学, 総合研究部, 助教 (80377514)
NOZAKI Yumi 山梨大学, 総合研究部, 助教 (80530104)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | hypoxia / TET2 / Wnt5 / JAK2V617F / Hypoxia / WNT5 / methylation / 低酸素応答 / 骨髄増殖性腫瘍 / JAK２変異 / エピゲノム / TETファミリー / 白血病 |
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| Outline of Final Research Achievements |
In the present study, we investigated the role of hypoxia on epigenetic gene regulation in cells derived from myeloproliferative neoplasms having active mutant form of JAK2, JAK2V617F. After culture at hypoxic conditions, total level of methylated cytosine levels were changed in the cells.5-hydorxy-methyl cytosine (5-hmC)levels were drastically decreased in SET-2 cells with normal TET2 function. In contrast, 5-hmC levels were not changed during treatment with hypoxia in HEL cells, which lack TET2 gene. We also found that methylation of promoter lesion of Wnt5a gene were decreased after hypoxia treatment. We also confirmed that hypoxia actually induced expression of Wnt5a both at mRNA and protein levels. Our observations suggested that hypoxia could regulate gene expression not only through activation of transcription factor, HIF, but also through modification of epigenomic machinery including TET2.
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