Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells

Immunity. 2018 Feb 20;48(2):243-257.e10. doi: 10.1016/j.immuni.2018.01.012.


T cell development is orchestrated by transcription factors that regulate the expression of genes initially buried within inaccessible chromatin, but the transcription factors that establish the regulatory landscape of the T cell lineage remain unknown. Profiling chromatin accessibility at eight stages of T cell development revealed the selective enrichment of TCF-1 at genomic regions that became accessible at the earliest stages of development. TCF-1 was further required for the accessibility of these regulatory elements and at the single-cell level, it dictated a coordinate opening of chromatin in T cells. TCF-1 expression in fibroblasts generated de novo chromatin accessibility even at chromatin regions with repressive marks, inducing the expression of T cell-restricted genes. These results indicate that a mechanism by which TCF-1 controls T cell fate is through its widespread ability to target silent chromatin and establish the epigenetic identity of T cells.

Keywords: Lineage-determining transcription factor; T cell development; TCF-1; chromatin accessibility; epigenetics; nucleosomes; repressed chromatin; reprogramming; single-cell epigenomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage*
  • Chromatin / physiology
  • Chromatin Assembly and Disassembly
  • Epigenomics*
  • Fibroblasts / metabolism
  • Hepatocyte Nuclear Factor 1-alpha / physiology*
  • Mice
  • NIH 3T3 Cells
  • T Cell Transcription Factor 1 / physiology*
  • T-Lymphocytes / physiology*
  • Transcription, Genetic


  • Chromatin
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • T Cell Transcription Factor 1