Interactions among the transcription factors Runx1, RORγt and Foxp3 regulate the differentiation of interleukin 17–producing T cells
F Zhang, G Meng, W Strober - Nature immunology, 2008 - nature.com
F Zhang, G Meng, W Strober
Nature immunology, 2008•nature.comThe molecular mechanisms underlying the differentiation of interleukin 17–producing T
helper cells (TH-17 cells) are still poorly understood. Here we show that optimal transcription
of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one
conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained
regions that bound the transcription factors RORγt and Runx1. Runx1 influenced TH-17
differentiation by inducing RORγt expression and by binding to and acting together with …
helper cells (TH-17 cells) are still poorly understood. Here we show that optimal transcription
of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one
conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained
regions that bound the transcription factors RORγt and Runx1. Runx1 influenced TH-17
differentiation by inducing RORγt expression and by binding to and acting together with …
Abstract
The molecular mechanisms underlying the differentiation of interleukin 17–producing T helper cells (TH-17 cells) are still poorly understood. Here we show that optimal transcription of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained regions that bound the transcription factors RORγt and Runx1. Runx1 influenced TH-17 differentiation by inducing RORγt expression and by binding to and acting together with RORγt during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on TH-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with RORγt regulates TH-17 differentiation.
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