CCCTC-Binding Factor and the Transcription Factor T-bet Orchestrate T Helper 1 Cell-Specific Structure and Function at the Interferon-γ Locus

Academic Article

Abstract

  • How cell type-specific differences in chromatin conformation are achieved and their contribution to gene expression are incompletely understood. Here we identify a cryptic upstream orchestrator of interferon-γ (IFNG) transcription, which is embedded within the human IL26 gene, compromised of a single CCCTC-binding factor (CTCF) binding site and retained in all mammals, even surviving near-complete evolutionary deletion of the equivalent gene encoding IL-26 in rodents. CTCF and cohesins occupy this element in vivo in a cell type-nonspecific manner. This element is juxtaposed to two other sites located within the first intron and downstream of Ifng, where CTCF, cohesins, and the transcription factor T-bet bind in a T helper 1 (Th1) cell-specific manner. These interactions, close proximity of other elements within the locus to each other and to the gene encoding interferon-γ, and robust murine Ifng expression are dependent on CTCF and T-bet. The results demonstrate that cooperation between architectural (CTCF) and transcriptional enhancing (T-bet) factors and the elements to which they bind is required for proper Th1 cell-specific expression of Ifng. © 2009 Elsevier Inc. All rights reserved.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Author List

  • Sekimata M; Pérez-Melgosa M; Miller SA; Weinmann AS; Sabo PJ; Sandstrom R; Dorschner MO; Stamatoyannopoulos JA; Wilson CB
  • Start Page

  • 551
  • End Page

  • 564
  • Volume

  • 31
  • Issue

  • 4