Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation
Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation
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DOI：
10.1073/pnas.1214682110
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发表时间：
2013-01-02
影响因子：
11.1
通讯作者：
Lee, Gap Ryol
中科院分区：
文献类型：
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作者：
Hwang, Soo Seok;Kim, Young Uk;Lee, Gap Ryol
Th2基因位点控制区(LCR)在Th2细胞分化过程中对细胞因子基因的高效和协调调控起着重要作用。然而，人们对此的分子机制知之甚少。为了研究Th2 LCR的分子机制，我们寻找了与其结合的蛋白质。我们发现转录因子YY1以Th2特异性的方式与LCR和整个Th2细胞因子基因座结合。逆转录病毒YY1过表达可诱导Th2细胞因子表达。在哮喘动物模型中，小鼠的CD4特异性YY1基因敲除导致Th2细胞因子表达显著减少，染色质重塑受到抑制，染色体内相互作用减少，抵抗力降低。YY1在物理上与GATA结合蛋白-3(GATA3)相关，是GATA3与该基因结合所必需的。在GATA3结合之前，YY1与基因座上的调控元件结合。因此，YY1与GATA3协同作用，是调节Th2细胞因子基因座和Th2细胞分化所必需的。
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.