Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment

Nat Immunol. 2017 Feb;18(2):173-183. doi: 10.1038/ni.3646. Epub 2016 Dec 19.


Most Foxp3+ regulatory T (Treg) cells develop in the thymus as a functionally mature T cell subpopulation specialized for immune suppression. Their cell fate appears to be determined before Foxp3 expression; yet molecular events that prime Foxp3- Treg precursor cells are largely obscure. We found that Treg cell-specific super-enhancers (Treg-SEs), which were associated with Foxp3 and other Treg cell signature genes, began to be activated in Treg precursor cells. T cell-specific deficiency of the genome organizer Satb1 impaired Treg-SE activation and the subsequent expression of Treg signature genes, causing severe autoimmunity due to Treg cell deficiency. These results suggest that Satb1-dependent Treg-SE activation is crucial for Treg cell lineage specification in the thymus and that its perturbation is causative of autoimmune and other immunological diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity
  • Cell Differentiation / immunology*
  • Cell Lineage
  • Cells, Cultured
  • Enhancer Elements, Genetic / genetics
  • Epigenesis, Genetic
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Immune Tolerance
  • Male
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Organ Specificity
  • Precursor Cells, T-Lymphoid / physiology
  • T-Lymphocytes, Regulatory / physiology*
  • Transcriptional Activation / immunology*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Matrix Attachment Region Binding Proteins
  • Satb1 protein, mouse