Oct-1 Regulates IL-17 Expression by Directing Interchromosomal Associations in Conjunction with CTCF in T Cells

LK Kim, E Esplugues, CE Zorca, F (Fabio) Parisi, Y Kluger, TH Kim, Niels Galjart, RA Flavell

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38 Citations (Scopus)

Abstract

Interchromosomal associations can regulate gene expression, but little is known about the molecular basis of such associations. In response to antigen stimulation, naive T cells can differentiate into Th1, Th2, and Th17 cells expressing IFN-gamma, IL-4, and IL-17, respectively. We previously reported that in naive T cells, the IIFN-gamma locus is associated with the Th2 cytokine locus. Here we show that the Th2 locus additionally associates with the IL-17 locus. This association requires a DNase I hypersensitive region (RHS6) at the Th2 locus. RHS6 and the IL-17 promoter both bear Oct-1 binding sites. Deletion of either of these sites or Oct-1 gene impairs the association. Oct-1 and CTCF bind their cognate sites cooperatively, and CTCF deficiency similarly impairs the association. Finally, defects in the association lead to enhanced IL-17 induction. Collectively, our data indicate Th17 lineage differentiation is restrained by the Th2 locus via interchromosomal associations organized by Oct-1 and CTCF.
Original languageUndefined/Unknown
Pages (from-to)56-66
Number of pages11
JournalMolecular Cell
Volume54
Issue number1
DOIs
Publication statusPublished - 2014

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