A Shared Regulatory Element Controls the Initiation of Tcf7 Expression During Early T Cell and Innate Lymphoid Cell Developments

Front Immunol. 2020 Mar 20:11:470. doi: 10.3389/fimmu.2020.00470. eCollection 2020.

Abstract

The transcription factor TCF-1 (encoded by Tcf7) plays critical roles in several lineages of hematopoietic cells. In this study, we examined the molecular basis for Tcf7 regulation in T cells, innate lymphoid cells, and migratory conventional dendritic cells that we find express Tcf7. We identified a 1 kb regulatory element crucial for the initiation of Tcf7 expression in T cells and innate lymphoid cells, but dispensable for Tcf7 expression in Tcf7-expressing dendritic cells. Within this region, we identified a Notch binding site important for the initiation of Tcf7 expression in T cells but not in innate lymphoid cells. Our work establishes that the same regulatory element is used by distinct transcriptional controllers to initiate Tcf7 expression in T cells and ILCs.

Keywords: T cells; TCF-1; Tcf7; development; enhancer; innate lymphoid cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression Regulation
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism*
  • Immunity, Innate
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Regulatory Elements, Transcriptional / genetics*
  • T-Lymphocytes / physiology*

Substances

  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse