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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation
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Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation

机译:转录因子YY1对于调节Th2细胞因子基因座和Th2细胞分化至关重要

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摘要

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.
机译:Th2基因座控制区(LCR)已被证明在Th2细胞分化过程中有效和协调的细胞因子基因调控中很重要。但是,对此的分子机理了解甚少。为了研究Th2 LCR的分子机制,我们搜索了与其结合的蛋白质。我们发现转录因子YY1以Th2特异性方式与LCR和整个Th2细胞因子基因座结合。逆转录病毒过表达的YY1诱导Th2细胞因子表达。小鼠中YY1的CD4特异性敲低导致Th2细胞因子表达显着降低,染色质重塑被抑制,染色体内相互作用降低以及哮喘动物模型中的抗性。 YY1与GATA结合蛋白3(GATA3)物理关联,是GATA3与基因座结合所必需的。在GATA3结合之前,YY1与基因座的调节元件结合。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。

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    Department of Life Science, Sogang University, Seoul, Korea 121-742;

    Department of Life Science, Sogang University, Seoul, Korea 121-742;

    Department of Life Science, Sogang University, Seoul, Korea 121-742;

    Department of Life Science, Sogang University, Seoul, Korea 121-742;

    Department of Life Science, Sogang University, Seoul, Korea 121-742;

    Department of Life Science, Sogang University, Seoul, Korea 121-742;

    Department of Life Science, Sogang University, Seoul, Korea 121-742;

    Department of Biological Sciences, Louisiana State University, Baton Rouge, LA;

    Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria;

    Research Institute of Molecular Pathology, Vienna Biocenter, A-1030 Vienna, Austria;

    Department of Life Science, Sogang University, Seoul, Korea 121-742;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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