CTCF and T-bet orchestrate Th1 T cell-specific structure and function at the interferon-γ locus

• Published in: Immunity (Cambridge, Mass.) Mass.), 2009-10, Vol.31 (4), p.551-564
• Main Authors: Sekimata, Masayuki, Pérez-Melgosa, Mercedes, Miller, Sara A., Weinmann, Amy S., Sabo, Peter J., Sandstrom, Richard, Dorschner, Michael O., Stamatoyannopoulos, John A., Wilson, Christopher B.
• Format: Article
• Language: English
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2009.08.021

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 CTCF-binding site and retained in all mammals, even surviving near-complete deletion of IL26 in rodents. CTCF and cohesins occupy this element in vivo in a cell-type non-specific manner. This element is approximated with two other sites located within the first intron and downstream of Ifng, where CTCF, cohesins and T-bet bind in a Th1-specific manner. These interactions, approximation of other elements within the locus to each other and to Ifng , and robust 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-specific expression of Ifng .