2004 Fiscal Year Final Research Report Summary
Regulation of transcription by heme with sperm reference to cell differentiation
| Project/Area Number |
14370048
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
FUJITA Hiroyoshi Hokkaido University, School of Medicine, Professor, 大学院・医学研究科, 教授 (60142931)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Atsushi Hokkaido University, School of Medicine, Associate Professor, 大学院・医学研究科, 講師 (50255436)
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| Project Period (FY) |
2002 – 2004
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| Keywords | heme / Bach1 / globin / erythrocyte / platelet / hypoxia |
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| Research Abstract |
We have investigated Bach1, the first found mammalian transcriptional factor that contains heme. Our previous investigations reveals that the factor contains one mole of heme per one subunit, and that the DNA binding activity of Bach1 is negatively regulated by heme saturation. In other words, heme saturated Bach1 lose its binding activity against MARE site resulting in an available MARE site for another transcriptional factors such as Nrf2, NFE2 and so on.
It has been, however, not yet well elucidated the genes that are under the negative control in Bach1/heme system. In the present study, we have examined if hens oxygenase-1 gene, the key enzyme of home catabolism, which is well known to activated by its substrate, is under the control of Bach1/heme system or not. As was already expected, our data is clearly indicated that heme oxygenase-1 gene was negatively regulated through Bach1 binding to MARE site. Hereby, we elucidated for the first time the precise mechanism of here mediated activation of gene that is physiologically important to metabolize a huge amount of heme, a biologically harmful pro-oxidant.
In addition to heme oxygenase-1 gene, we have examined the regulation of beta-globin gene. It is well known that heme and globin syntheses for hemoglobin are coordinated ; i.e., there are no exceeded syntheses for heme and globin. The mechanism to regulate equal mole of heme and globin has not been well understood. Bach1 is one of the most possible mechanisms to control hemoglobin formation. Indeed, our observations demonstrated that MEAR site in globin gene ruled heme mediated upregulation via the loss of Bach1 binding activity. Thus, we can biosynthesize globin protein just equal to home in differentiating erythroid cells. In this way, we are free form dangerous pro-oxidant, heme, even through erythroid differentiation.
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[Journal Article] WAVE/Scars in Platelets.2005
Author(s)
Oda A, Miki H, Wada I, Yamaguchi H, Yamazaki D, Suetsugu S, Nakajima M, Nakayama A, Okawa K, Miyazaki H, Matsuno K, Ochs HD, Machesky LM, Fujita H, Takenawa T
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] CrkL directs ASAP1 to preripheral focal adhesions.2003
Author(s)
Oda A, Wada I, Miura K, Okawa K, Kadoya T, Kadoya T, Kato T, Nishihara H, Maeda M, Tanaka S, Nagashima K, Nishitani C, Masuno K, Ishino M, Machesky LM, Randazzo P, Fujita H
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Journal Title
J Biol Chem 278
Pages: 6456-6460
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bach 1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells.2003
Author(s)
Kitamuro T, Takahashi K, Ogawa K, Udono RF, Takeda K, Furuyama K, Nakayama M, Sun J, Fujita H, Hida W, Hattori T, Shirato K, Igarashi K, Shibahara S
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Journal Title
J Biol Chem 278
Pages: 9125-9133
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Erythropoietin regulates tumor growth of human malignancies.32003
Author(s)
Yasuda Y, Fujita Y, Matsuo T, Koinuma S, Hara S, Tazaki A, Onozaki M, Hashimoto M, Musha T, Ogawa K, Fujita H, Nakamura Y, Shiozaki H, Utsumi H
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Journal Title
Carcinogenesis 24
Pages: 1021-1029
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A functional role of Stat3 in vivo megakaryopoiesis.2002
Author(s)
Kirito K, Osawa M, Morita H, Shimizu R, Yamamoto M, Oda A, Fujita H, Tanaka M, Nakajima K, Miura Y, Ozawa K, Komatsu N
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Journal Title
Blood 99
Pages: 3220-3227
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Erythropoietin is involved in growth and angiogenesis in malignant tumors of emale reproductive organs.2002
Author(s)
Yasuda Y, Fujita Y, Masuda S, Musha T, Ueda K, Tanaka H, Fujita H, Matsuo T, Nagao M, Sasaki R, Nakamura Y
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Journal Title
Carcinogenesis 23
Pages: 1797-1805
Description
「研究成果報告書概要(欧文)」より
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