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

 Lark Kyun Kim  ;  Enric Esplugues  ;  Cornelia E. Zorca  ;  Niels J. Galjart  ;  Richard A. Flavell 
 MOLECULAR CELL, Vol.54(1) : 56-66, 2014 
Journal Title
Issue Date
Animals ; Binding Sites ; CCCTC-Binding Factor ; Cell Differentiation ; Cell Lineage ; Cells, Cultured ; Chromosomes, Mammalian* ; Deoxyribonuclease I/metabolism ; Gene Expression Regulation ; Genes, Reporter ; Genetic Loci ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Interleukin-17/genetics ; Interleukin-17/metabolism* ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Octamer Transcription Factor-1/deficiency ; Octamer Transcription Factor-1/genetics ; Octamer Transcription Factor-1/metabolism* ; Promoter Regions, Genetic ; Repressor Proteins/genetics ; Repressor Proteins/metabolism* ; Sequence Deletion ; Th17 Cells/immunology ; Th17 Cells/metabolism* ; Th2 Cells/immunology ; Th2 Cells/metabolism* ; Time Factors
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-γ, IL-4, and IL-17, respectively. We previously reported that in naive T cells, the IFN-γ 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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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Lark Kyun(김락균) ORCID logo https://orcid.org/0000-0001-5983-4470
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