Essential Roles of SATB1 in Specifying T Lymphocyte Subsets

Publication date: 9 May 2017
Source:Cell Reports, Volume 19, Issue 6
Author(s): 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
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.

Graphical abstract

Teaser

Kakugawa et al. demonstrate that differentiation of MHC class I- and II-selected thymocytes into cytotoxic and helper lineage in the thymus is severely impaired by the lack of SATB1 function in part due to the inappropriate activation of lineage-specifying genes, such as Thpok, Runx3, Cd4, and Cd8.


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