CRTAM is negatively regulated by ZEB1 in T cells

Mol Immunol. 2015 Aug;66(2):290-8. doi: 10.1016/j.molimm.2015.03.253. Epub 2015 Apr 21.

Abstract

T cell activation leads to the induction of genes that are required for appropriate immune responses. This includes CRTAM (Class-I MHC-restricted T cell associated molecule), a protein that plays a key role in T cell development, proliferation, and generating cell polarity during activation. We previously characterized the CRTAM promoter and described how AP-1 family members are important for inducing CRTAM expression upon antigenic activation. Here, we show that CRTAM is a molecular target for ZEB1 (zinc finger E-box-binding protein), a homeodomain/Zn finger transcription factor. Overexpression of ZEB1 repressed CRTAM promoter activity, as well as endogenous CRTAM levels in human T cells. ZEB1-mediated transcriptional repression was abolished when E-box-like elements in the CRTAM promoter are mutated. In summary, ZEB1 functions as a transcriptional repressor for the CRTAM gene in both non-stimulated and stimulated T cells, thereby modulating adaptive immune responses.

Keywords: CRTAM; E-box-like elements; Promoter; Repression; Transcription; ZEB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Binding Sites
  • Gene Expression Regulation / immunology*
  • Genes, Reporter
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / immunology
  • Humans
  • Immunoglobulins / genetics*
  • Immunoglobulins / immunology
  • Jurkat Cells
  • Luciferases / genetics
  • Luciferases / metabolism
  • Lymphocyte Activation
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Promoter Regions, Genetic
  • Protein Binding
  • Signal Transduction
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / immunology
  • Transcription Factors / genetics*
  • Transcription Factors / immunology
  • Transcription, Genetic
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Homeodomain Proteins
  • Immunoglobulins
  • NF-kappa B
  • Transcription Factor AP-1
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • class-I restricted T cell-associated molecule
  • Luciferases