Essential Roles of SATB1 in Specifying T Lymphocyte Subsets

Kiyokazu Kakugawa, Satoshi Kojo, Hirokazu Tanaka, Wooseok Seo, Takaho A. Endo, Yohko Kitagawa, Sawako Muroi, Mari Tenno, Nighat Yasmin, Yoshinori Kohwi, Shimon Sakaguchi, Terumi Kowhi-Shigematsu, Ichiro Taniuchi

研究成果: Contribution to journalArticle査読

39 被引用数 (Scopus)

抄録

T cell receptor (TCR) signaling by MHC class I and II induces thymocytes to acquire cytotoxic and helper fates via the induction of Runx3 and ThPOK transcription factors, respectively. The mechanisms by which TCR signaling is translated into transcriptional programs for each cell fate remain elusive. Here, we show that, in post-selection thymocytes, a genome organizer, SATB1, activates genes for lineage-specifying factors, including ThPOK, Runx3, CD4, CD8, and Treg factor Foxp3, via regulating enhancers in these genes in a locus-specific manner. Indeed, SATB1-deficient thymocytes are partially re-directed into inappropriate T lineages after both MHC class I- and II-mediated selection, and they fail to generate NKT and Treg subsets. Despite its essential role in activating enhancers for the gene encoding ThPOK in TCR-signaled thymocytes, SATB1 becomes dispensable for maintaining ThPOK in CD4+ T cells. Collectively, our findings demonstrate that SATB1 shapes the primary T cell pool by directing lineage-specific transcriptional programs in the thymus.

本文言語英語
ページ(範囲)1176-1188
ページ数13
ジャーナルCell Reports
19
6
DOI
出版ステータス出版済み - 5 9 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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