E proteins orchestrate dynamic transcriptional cascades implicated in the suppression of the differentiation of group 2 innate lymphoid cells

J Biol Chem. 2020 Oct 30;295(44):14866-14877. doi: 10.1074/jbc.RA120.013806. Epub 2020 Aug 19.


Group 2 innate lymphoid cells (ILC2s) represent a subset of newly discovered immune cells that are involved in immune reactions against microbial pathogens, host allergic reactions, as well as tissue repair. The basic helix-loop-helix transcription factors collectively called E proteins powerfully suppress the differentiation of ILC2s from bone marrow and thymic progenitors while promoting the development of B and T lymphocytes. How E proteins exert the suppression is not well understood. Here we investigated the underlying molecular mechanisms using inducible gain and loss of function approaches in ILC2s and their precursors, respectively. Cross-examination of RNA-seq and ATAC sequencing data obtained at different time points reveals a set of genes that are likely direct targets of E proteins. Consequently, a widespread down-regulation of chromatin accessibility occurs at a later time point, possibly due to the activation of transcriptional repressor genes such as Cbfa2t3 and Jdp2 The large number of genes repressed by gain of E protein function leads to the down-regulation of a transcriptional network important for ILC2 differentiation.

Keywords: E2A; HEB; ILC2; MTG16; basic helix-loop-helix transcription factor (bHLH); innate immunity; innate lymphoid cells; lymphocyte; repressor protein; transcription factor.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Chromatin / metabolism
  • Gene Expression
  • Gene Regulatory Networks*
  • Immunity, Innate*
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Mice


  • Basic Helix-Loop-Helix Transcription Factors
  • Chromatin