In vivo role of transcriptional elongation/ubiquitin ligase factor Elongin
Project/Area Number |
24590357
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General medical chemistry
|
Research Institution | Kochi University |
Principal Investigator |
ASO Teijiro 高知大学, 教育研究部医療学系, 教授 (20291289)
|
Co-Investigator(Renkei-kenkyūsha) |
KITAJIMA Shigetaka 東京医科歯科大学, 難治疾患研究所, 教授 (30186241)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | Elongin / 転写伸長 / ユビキチンリガーゼ / RNAポリメラーゼII / 神経分化 / 遺伝子発現 / 神経堤 / RNA sequence / ChIP / 遺伝子ノックアウト / ノックアウトマウス |
Outline of Final Research Achievements |
Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A-/-) embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A-/- embryonic stem cells (ESCs) show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the above activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced up-regulation of a subset of neurogenesis-related genes in Elongin A-/- ESCs.
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Transcriptional elongation factor elongin A regulates retinoic acid-induced gene expression during neuronal differentiation.2012
Author(s)
Yasukawa T, Bhatt S, Takeuchi T, Kawauchi J, Takahashi H, Tsutsui A, Muraoka T, Inoue M, Tsuda M, Kitajima S, Conaway RC, Conaway JW, Trainor PA, Aso T.
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Journal Title
Cell Rep
Volume: 2(5)
Issue: 5
Pages: 1129-36
DOI
Related Report
Peer Reviewed
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[Presentation] 転写伸長因子Elongin Aの標的遺伝子の網羅的探索2014
Author(s)
安川 孝史, 筒井 文, 村岡 拓也, 佐藤 チエリ, 佐藤 滋生, Conaway Ronald C, Conaway Joan W, 北嶋 繁孝, 麻生 悌二郎
Organizer
第37回日本分子生物学会年会
Place of Presentation
横浜(パシフィコ横浜)
Year and Date
2014-11-25 – 2014-11-27
Related Report
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[Presentation] 感覚神経系の発生・分化におけるElongin Aの標的遺伝子の同定2014
Author(s)
安川 孝史, 村岡 拓也, 筒井 文, 佐藤 チエリ, 佐藤 滋生, 川内 潤也, 井上 允, 北嶋 繁孝, Conaway Ronald C, Conaway Joan W, 麻生 悌二郎
Organizer
第87回日本生化学会大会
Place of Presentation
京都(国立京都国際会館)
Year and Date
2014-10-15 – 2014-10-18
Related Report
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[Presentation] Transcriptional Properties of Mammalian Elongin A and Its Role in Stress Response.2012
Author(s)
Makoto Inoue, Kawauchi, J., Tanaka, Y., Yasukawa, T., Aso, T., Kitajima, S.
Organizer
第35回日本分子生物学会年会
Place of Presentation
マリンメッセ福岡(福岡県)
Related Report