Article abstract


Nature Immunology 8, 732 - 742 (2007)
Published online: 3 June 2007 | Corrected online: 5 July 2007 | Corrected online: 16 November 2007 | doi:10.1038/ni1474



There is a Corrigendum (December 2007) associated with this Article.

There is a Corrigendum (January 2008) associated with this Article.

Comprehensive epigenetic profiling identifies multiple distal regulatory elements directing transcription of the gene encoding interferon-big gamma

Jamie R Schoenborn1,2, Michael O Dorschner3,4,6, Masayuki Sekimata1,6, Deanna M Santer1, Maria Shnyreva1, David R Fitzpatrick5, John A Stamatoyannopoulos3,4 & Christopher B Wilson1


Unlike the well defined T helper type 2 cytokine locus, little is known about the regulatory elements that govern the expression of Ifng, which encodes the 'signature' T helper type 1 cytokine interferon-gamma. Here our evolutionary analysis showed that the mouse Ifng locus diverged from the ancestral locus as a result of structural rearrangements producing deletion of the neighboring gene encoding interleukin 26 and disrupting synteny 57 kilobases upstream of Ifng. Proximal to that disruption, we identified by high-resolution mapping many regions with CD4+ T cell subset–specific epigenetic modifications. A subset of those regions represented enhancers, whereas others blocked the activity of upstream enhancers or insulated Ifng from neighboring chromatin. Our findings suggest that proper expression of Ifng is maintained through the collective action of multiple distal regulatory elements present in a region of about 100 kilobases flanking Ifng.

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  1. Department of Immunology, University of Washington, Seattle, Washington 98195, USA.
  2. Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington 98195, USA.
  3. Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
  4. Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
  5. PO Box 270514, Fort Collins, Colorado 80527, USA.
  6. These authors contributed equally to this work.

Correspondence to: Christopher B Wilson1 e-mail: cbwilson@u.washington.edu

* In the version of this article initially published, the surname of the penultimate author is misspelled. The correct spelling is Stamatoyannopoulos. The error has been corrected in the HTML and PDF versions of the article.

** In the version of this article initially published, labels in Figures 2 and 4 are incorrect (as is the relevant text for Figure 4), and a reagent is incorrectly identified in Methods. In Figure 2, the label "IfngCNS+54" should be "IfngCNS+55." For Figure 4, the primers used to analyze the intronic region of Ifng for CpG methylation after bisulfite treatment amplify intron 1; thus, the label above the sixth column in Figure 4a should be "Ifng intron 1" and the accompanying text on page 736, column 1, should read "intron 1" on lines 3 and 13. In the Methods section, page 740 column 2, the end of line 23 should read "rabbit immunoglobulin G." The errors have been corrected in the PDF version of the article.

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