Regulation of helper/cytotoxic lineage choice by chromatin structures

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293109
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Taniuchi Ichiro 国立研究開発法人理化学研究所, 統合生命医科学研究センター, グループディレクター (20284573)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: T細胞分化 / 転写因子 / クロマチン

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.

Free Research Field

分子免疫学