Essential Roles of SATB1 in Specifying T Lymphocyte Subsets

Cell Rep. 2017 May 9;19(6):1176-1188. doi: 10.1016/j.celrep.2017.04.038.


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.

Keywords: SATB1; T lymphocyte development; gene regulation; genome organizer; lineage specification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / genetics
  • CD4 Antigens / metabolism
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • Cell Lineage
  • Core Binding Factor Alpha 3 Subunit / genetics
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Enhancer Elements, Genetic
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Lymphopoiesis*
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Mice
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation


  • CD4 Antigens
  • CD8 Antigens
  • Core Binding Factor Alpha 3 Subunit
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Matrix Attachment Region Binding Proteins
  • Runx3 protein, mouse
  • Satb1 protein, mouse
  • Th-POK protein, mouse
  • Transcription Factors