Identification of novel transcriptional factors and their roles for homeostasis of lipid composition of cell membrane
Project/Area Number |
24590358
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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
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Research Institution | Dokkyo Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
AOYAMA Chieko 獨協医科大学, 医学部, 助教 (90420778)
SATOU Motoyasu 獨協医科大学, 医学部, 助教 (20418891)
HORIBATA Yasuhiro 獨協医科大学, 医学部, 助教 (80392116)
ANDO Hiromi 獨協医科大学, 医学部, 助教 (10704885)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | オキシステロール / ホスホエタノールアミン / シチジリルトランスフェラーゼ / HMG-CoAレダクターゼ / NF-Y / 25-ヒドロキシコレステロール / ホスファチジルエタノールアミン / コレステロール / Yin Yang1 / Phosphatidylethanolamine / CTP:phosphoethanolamine / Cytidylyltransferase / 25-hydroxycholesterol / HMG-CoA reductase / YY1 |
Outline of Final Research Achievements |
ET (CTP:phosphoethanolamine cytidylyltransferase) is the rate-limiting enzyme in mammalian PE (phosphatidylethanolamine) synthesis. We found that ET mRNAlevels increased in cells after serum starvation, an effect that could be suppressed by low-density lipoprotein or 25-HC (25-hydroxycholesterol). Transcription of Hmgcr, which encodes 3-hydroxy-3-methylglutaryl-CoA reductase, is also suppressed by 25-HC. Nevertheless, a sterol-regulatory element was not detected in the Pcyt2 promoter region. The important element for transcriptional control of ET by 25-HC (1.25 μM) was determined to reside between -56 and -36 and NF-Y (nuclear factor-Y) binds the site. Moreover, NF-Y binds to the Hmgcr promoter in gel-shift analysis. ChIP analysis revealed that 25-HC inhibited the interaction between NF-Y and RNA polymerase II on the Pcyt2 and Hmgcr promoters. We conclude that NF-Y is important for the basal transcription of Pcyt2 and is involved in the inhibitory effects of 25-HC.
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Report
(5 results)
Research Products
(21 results)
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[Journal Article] Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: Extending the clinical and pathological phenotype2013
Author(s)
Ros Quinlivan, Satomi Mitsuahashi, Caroline Sewry, Sebahattin Cirak, Chieko Aoyama, David Mooore, Stephen Abbs, Stephanie Robb, Tina Newton, Celia Moss, Daniel Birchall, Hiroyuki Sugimoto, Kate Bushby, Michela Guglieri, Francesco Muntoni, Ichizo Nishino, Volker Straub
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Journal Title
Neuromusucular Disorders
Volume: 23
Issue: 7
Pages: 549-556
DOI
Related Report
Peer Reviewed
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