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Publication : Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells.

First Author  Kim LK Year  2014
Journal  Mol Cell Volume  54
Issue  1 Pages  56-66
PubMed ID  24613343 Mgi Jnum  J:212499
Mgi Id  MGI:5581577 Doi  10.1016/j.molcel.2014.02.004
Citation  Kim LK, et al. (2014) Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells. Mol Cell 54(1):56-66
abstractText  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 IFN-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.
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