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论文题目: Cross Talk between Histone Deacetylase 4 and STAT6 in the Transcriptional Regulation of Arginase 1 during Mouse Dendritic Cell Differentiation
英文论文题目: Cross Talk between Histone Deacetylase 4 and STAT6 in the Transcriptional Regulation of Arginase 1 during Mouse Dendritic Cell Differentiation
第一作者: Yang, Q; Wei, JY; Zhong, LM; Shi, MH; Zhou, P; Zuo, SK; Wu, K; Zhu, MJ; Huang, X; Yu, Y; Zhang, H; Yin, HY; Zhou, J
英文第一作者: Yang, Q; Wei, JY; Zhong, LM; Shi, MH; Zhou, P; Zuo, SK; Wu, K; Zhu, MJ; Huang, X; Yu, Y; Zhang, H; Yin, HY; Zhou, J
联系作者: Zhou, J (reprint author), Sun Yat Sen Univ, Zhongshan Sch Med, Inst Human Virol, Guangzhou 510275, Guangdong, Peoples R China.
英文联系作者: Zhou, J (reprint author), Sun Yat Sen Univ, Zhongshan Sch Med, Inst Human Virol, Guangzhou 510275, Guangdong, Peoples R China.
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发表年度: 2015
卷: 35
期: 1
页码: 63-75
摘要: L-Arginine and L-arginine-metabolizing enzymes play important roles in the biology of some types of myeloid cells, including macrophage and myeloid-derived suppressor cells. In this study, we found evidence that arginase 1 (Arg1) is required for the differentiation of mouse dendritic cells (DCs). Expression of Arg1 was robustly induced during monocyte-derived DC differentiation. Ectopic expression of Arg1 significantly promoted monocytic DC differentiation in a granulocyte-macrophage colony-stimulating factor culture system and also facilitated the differentiation of CD8 alpha(+) conventional DCs in the presence of Flt3 ligand. Knockdown of Arg1 reversed these effects. Mechanistic studies showed that the induced expression of Arg1 in differentiating DCs was caused by enhanced recruitment of histone deacetylase 4 (HDAC4) to the Arg1 promoter region, which led to a reduction in the acetylation of both the histone 3 and STAT6 proteins and subsequent transcriptional activation of Arg1. Further investigation identified a novel STAT6 binding site within the Arg1 promoter that mediated its regulation by STAT6 and HDAC4. These observations suggest that the cross talk between HDAC4 and STAT6 is an important regulatory mechanism of Arg1 transcription in DCs. Moreover, overexpression of Arg1 clearly abrogated the ability of HDAC inhibitors to suppress DC differentiation. In conclusion, we show that Arg1 is a novel regulator of myeloid DC differentiation.
英文摘要: L-Arginine and L-arginine-metabolizing enzymes play important roles in the biology of some types of myeloid cells, including macrophage and myeloid-derived suppressor cells. In this study, we found evidence that arginase 1 (Arg1) is required for the differentiation of mouse dendritic cells (DCs). Expression of Arg1 was robustly induced during monocyte-derived DC differentiation. Ectopic expression of Arg1 significantly promoted monocytic DC differentiation in a granulocyte-macrophage colony-stimulating factor culture system and also facilitated the differentiation of CD8 alpha(+) conventional DCs in the presence of Flt3 ligand. Knockdown of Arg1 reversed these effects. Mechanistic studies showed that the induced expression of Arg1 in differentiating DCs was caused by enhanced recruitment of histone deacetylase 4 (HDAC4) to the Arg1 promoter region, which led to a reduction in the acetylation of both the histone 3 and STAT6 proteins and subsequent transcriptional activation of Arg1. Further investigation identified a novel STAT6 binding site within the Arg1 promoter that mediated its regulation by STAT6 and HDAC4. These observations suggest that the cross talk between HDAC4 and STAT6 is an important regulatory mechanism of Arg1 transcription in DCs. Moreover, overexpression of Arg1 clearly abrogated the ability of HDAC inhibitors to suppress DC differentiation. In conclusion, we show that Arg1 is a novel regulator of myeloid DC differentiation.
刊物名称: MOLECULAR AND CELLULAR BIOLOGY
英文刊物名称: MOLECULAR AND CELLULAR BIOLOGY
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学科: Biochemistry & Molecular Biology; Cell Biology
英文学科: Biochemistry & Molecular Biology; Cell Biology
影响因子: 4.777
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论文类别: Article
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