| Project/Area Number |
23390068
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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 |
General medical chemistry
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| Research Institution | Shiga University of Medical Science (2013)
Kyoto University (2011-2012) |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
IKAWA Tomokatsu 理化学研究所 統合生命医科学研究センター, 免疫細胞再生研究YCIラボ, 研究員 (60450392)
SATOH Fumiaki 京都大学, 医学研究科, 准教授 (20467426)
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2011: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | 染色体ダイナミクス / エピジェネティクス / コヒーシン / Rad21 / CTCF / E2A / ChIP-Seq / 染色体構造変化 / インシュレーター / クロマチン / 遺伝子発現 / 3C アッセイ / Mediator / 造血系前駆細胞 |
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| Outline of Final Research Achievements |
Cohesin essential for chromosome cohesion and the insulator component CTCF regulate the expression of genes, which are critical for cell differentiation, by chromosome dynamics. To identify genes that are regulated by these proteins and also critical for T cell differentiation, we performed ChIP-Seq analyses using the EBF-KO progenitor cell line, which differentiates to T cells upon Notch stimulation, and found that the cohesin subunit Rad21 and CTCF bound to the genes such as Tcf7 and Bcl11b, master regulators of T cell differentiation. We thus depleted Rad21 and CTCF by knockdown and found that Tcf7 and Bcl11b expression was further increased and T cell differentiation was facilitated. In contrast, when we depleted E2A essential for TCRβ locus contraction, Bcl11b and Notch target genes were downregulated and T cell differentiation was abrogated. These results suggest that Rad21/CTCF and E2A regulate T cell differentiation in a negative or positive manner, respectively.
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