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Nat Immunol. 2007 Jul;8(7):732-42. Epub 2007 Jun 3.

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

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1
Department of Immunology, University of Washington, Seattle, Washington 98195, USA.

Erratum in

  • Nat Immunol. 2008 Jan;9(1):105.
  • Nat Immunol. 2007 Aug;8(8):893. Stamatoyonnapoulos, John A [corrected to Stamatoyannopoulos, John A].

Abstract

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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PMID:
17546033
PMCID:
PMC2144744
DOI:
10.1038/ni1474
[Indexed for MEDLINE]
Free PMC Article
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