Essential Roles of SATB1 in Specifying T Lymphocyte Subsets.

Cell Reports
Kiyokazu KakugawaIchiro Taniuchi

Abstract

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.

Citations

Apr 21, 2018·Annual Review of Immunology·Ichiro Taniuchi
Nov 11, 2018·Oncogene·Rutika Naik, Sanjeev Galande
Jul 27, 2018·The Journal of Experimental Medicine·Shaojun XingHai-Hui Xue
Mar 16, 2019·Frontiers in Immunology·Emily A VoigtGregory A Poland
Jul 19, 2020·Science Immunology·Lawrence P AndrewsDario A A Vignali
Mar 3, 2018·Clinical & Translational Immunology·Timothy SadlonSimon C Barry
May 28, 2019·Cancer Cell International·Xiaodan LuoLian Liu
Sep 7, 2018·Nature Communications·Satoshi KojoIchiro Taniuchi
Jun 26, 2020·Nature Reviews. Immunology·Daniel G PellicciStuart P Berzins
May 18, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Krishna P SunkaraMary Bebawy
Dec 29, 2020·Nucleus·Tomas Zelenka, Charalampos Spilianakis
Feb 18, 2018·Current Opinion in Immunology·Mihalis Verykokakis, Barbara L Kee
Jun 1, 2021·Frontiers in Immunology·Laurianne ScourzicEffie Apostolou
Feb 23, 2021·Genome Génome / Conseil National De Recherches Canada·Delong FengBingtao Hao
Jun 21, 2021·The Journal of Molecular Diagnostics : JMD·Fanny DrieuxPhilippe Gaulard

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