A Distal Conserved Sequence Element Controls Ifng Gene Expression by T Cells and NK Cells

Academic Article

Abstract

  • 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. © 2006 Elsevier Inc. All rights reserved.
  • Digital Object Identifier (doi)

    Author List

  • Hatton RD; Harrington LE; Luther RJ; Wakefield T; Janowski KM; Oliver JR; Lallone RL; Murphy KM; Weaver CT
  • Start Page

  • 717
  • End Page

  • 729
  • Volume

  • 25
  • Issue

  • 5