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Publication : Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation.

First Author  Hwang SS Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  1 Pages  276-81
PubMed ID  23248301 Mgi Jnum  J:192524
Mgi Id  MGI:5465340 Doi  10.1073/pnas.1214682110
Citation  Hwang SS, et al. (2013) Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation. Proc Natl Acad Sci U S A 110(1):276-81
abstractText  The Th2 locus control region (LCR) has been shown to be important in efficient and coordinated cytokine gene regulation during Th2 cell differentiation. However, the molecular mechanism for this is poorly understood. To study the molecular mechanism of the Th2 LCR, we searched for proteins binding to it. We discovered that transcription factor YY1 bound to the LCR and the entire Th2 cytokine locus in a Th2-specific manner. Retroviral overexpression of YY1 induced Th2 cytokine expression. CD4-specific knockdown of YY1 in mice caused marked reduction in Th2 cytokine expression, repressed chromatin remodeling, decreased intrachromosomal interactions, and resistance in an animal model of asthma. YY1 physically associated with GATA-binding protein-3 (GATA3) and is required for GATA3 binding to the locus. YY1 bound to the regulatory elements in the locus before GATA3 binding. Thus, YY1 cooperates with GATA3 and is required for regulation of the Th2 cytokine locus and Th2 cell differentiation.
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