A distal conserved sequence element controls Ifng gene expression by T cells and NK cells

Immunity. 2006 Nov;25(5):717-29. doi: 10.1016/j.immuni.2006.09.007. Epub 2006 Oct 26.


Chromatin dynamics that regulate Ifng gene expression are incompletely understood. By using cross-species comparative sequence analyses, we have identified conserved noncoding sequences (CNSs) upstream of the Ifng gene, one of which, located -22 kb from the transcriptional start site, contains clustered consensus binding sequences of transcription factors that function in T cell differentiation. CNS-22 was uniquely associated with histone modifications typical of accessible chromatin in both T helper 1 (Th1) and Th2 cells and demonstrated significant and selective T-bet (T-box transcription factor expressed in T cells, Tbx21)-dependent binding and enhancer activity in Th1 cells. Deletion of CNS-22 in the context of an Ifng reporter transgene ablated T cell receptor-dependent and -independent Ifng expression in Th1 effectors and similarly blocked expression by cytotoxic T lymphocytes and natural killer cells. Thus, a single distal element may be essential for Ifng gene expression by both innate and adaptive immune effector cell lineages.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cattle
  • Cell Differentiation / immunology
  • Chickens
  • Chromosomes, Artificial, Bacterial / genetics
  • Conserved Sequence / genetics*
  • Gene Expression / immunology*
  • Gene Expression Regulation / immunology*
  • Histones / metabolism
  • Interferon-gamma / genetics*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Opossums
  • Polymerase Chain Reaction
  • Rats
  • Regulatory Elements, Transcriptional / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*


  • Histones
  • Interferon-gamma