2017 Fiscal Year Final Research Report
Regulation of erythropoiesis and macrophages by the heme signal
| Project/Area Number |
15H02506
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
張替 秀郎 東北大学, 医学系研究科, 教授 (50302146)
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUI Miki 東北大学, 医学系研究科, JSPS特別研究員(RPD) (00455784)
SAIGUSA Daisuke 東北大学, 東北メディカル・メガバンク機構, 助教 (90545237)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | ヘム / Bach1 / 赤血球 / マクロファージ / 質量分析 |
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| Outline of Final Research Achievements |
We reported previously that heme binds to the transcription factors Bach1 and Bach2 to regulate gene expression. In this study, we have successfully established the regulatory roles and biological significances of the heme-mediated regulation of these transcription factors.
We found that, unlike known heme-binding proteins, the heme-binding region of Bach2 is structurally disordered, and that this region remained disordered even in the presence of heme. Nonetheless, heme induced an interaction of Bach2 and protein kinase, which then phosphorylated Bach2. We also found that Bach1 was critical for adaptation of erythroid cells to iron deficiency. Bach1 kept expression of key erythroid transcription factor genes under such conditions. In stem and progenitor cells, Bach2 and Bach1 were found to promote lymphoid cell differentiation by restricting the expression of myeloid transcription factors as well as their target genes important for myeloid cell differentiation.
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| Free Research Field |
医歯薬学
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