生物
HDAC1型
HDAC4型
精氨酸酶
细胞分化
细胞生物学
转录因子
组蛋白脱乙酰基酶
STAT6
异位表达
基因敲除
组蛋白
细胞培养
精氨酸
生物化学
遗传学
基因
氨基酸
作者
Quan Yang,Jianyang Wei,Limei Zhong,Maohua Shi,Pan Zhou,Shengkai Zuo,Kang Wu,Mingjiang Zhu,Xi Huang,Ying Yu,Hui Zhang,Huiyong Yin,Jie Zhou
摘要
ABSTRACT 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 CD8α + 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI