| Budget Amount *help |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Outline of Final Research Achievements |
Helper versus cytotoxic lineage choice by T lymphocyte precursors serves as a good model to investigate how external environmental cue, TCR signals in this case, is integrated into genetic programming that govern cell fates. Since regulation of Thpok gene is a key to segregate these two fates, we examined how Thpok is regulated.
By using insertion ChIP, we found that cis-regulatory regions in the Thpok gene is assembled into the close proximity specifically in cytotoxic lineage. We also revealed that priming of Thpok gene by Bcl11b transcription factor, more specifically its C-terminal end Zinc-finger motif, during early thymocyte differentiation is essential for later coupling of TCR signals with appropriate Thpok expression. Lastly, our data unraveled that a genome organizer SATB1 plays essential roles in regulating expression of lineage specifying genes such as Thpok, Runx3 and Foxp3, to specify effect tor T cell subset.
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