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Publication : YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity.

First Author  Hwang SS Year  2016
Journal  Nat Commun Volume  7
Pages  10789 PubMed ID  26892542
Mgi Jnum  J:234737 Mgi Id  MGI:5790759
Doi  10.1038/ncomms10789 Citation  Hwang SS, et al. (2016) YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity. Nat Commun 7:10789
abstractText  Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) cells than T(conv) cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in T(reg) cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T(reg) cells by blocking Foxp3.
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