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Publication : Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells.

First Author  Zhang F Year  2008
Journal  Nat Immunol Volume  9
Issue  11 Pages  1297-306
PubMed ID  18849990 Mgi Jnum  J:141109
Mgi Id  MGI:3815380 Doi  10.1038/ni.1663
Citation  Zhang F, et al. (2008) Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat Immunol 9(11):1297-306
abstractText  The molecular mechanisms underlying the differentiation of interleukin 17-producing T helper cells (T(H)-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 RORgammat and Runx1. Runx1 influenced T(H)-17 differentiation by inducing RORgammat expression and by binding to and acting together with RORgammat during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on T(H)-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with RORgammat regulates T(H)-17 differentiation.
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