Yu Hong-Bing, Yurieva Marina, Balachander Akhila, Foo Ivy, Leong Xiangrong, Zelante Teresa, Zolezzi Francesca, Poidinger Michael, Ricciardi-Castagnoli Paola
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
Nucleic Acids Res. 2015 Jan;43(2):836-47. doi: 10.1093/nar/gku1369. Epub 2014 Dec 30.
The transcription factor NFATc2 regulates dendritic cell (DC) responses to microbial stimulation through the C-type lectin receptor dectin-1. But the genetic targets of NFATc2 and their effects on DC function remain largely unknown. Therefore we used ChIP-seq to conduct genome-wide mapping of NFATc2 target sites in dectin-1-activated DCs. By combining binding-site data with a comprehensive gene expression profile, we found that NFATc2 occupancy regulates the expression of a subset of dectin-1-activated genes. Surprisingly, NFATc2 targeted an extensive range of DC-derived cytokines and chemokines, including regulatory cytokines such as IL2, IL23a and IL12b. Furthermore, we demonstrated that NFATc2 binding is required to induce the histone 3 lysine 4 trimethylation (H3K4me3) epigenetic mark, which is associated with enhanced gene expression. Together, these data show that the transcription factor NFATc2 mediates epigenetic modification of DC cytokine and chemokine genes leading to activation of their expression.
转录因子NFATc2通过C型凝集素受体dectin-1调节树突状细胞（DC）对微生物刺激的反应。但NFATc2的基因靶点及其对DC功能的影响仍 largely未知。因此，我们使用ChIP-seq对dectin-1激活的DC中NFATc2靶点进行全基因组定位。通过将结合位点数据与全面的基因表达谱相结合，我们发现NFATc2的占据调节了dectin-1激活基因子集的表达。令人惊讶的是，NFATc2靶向多种DC衍生的细胞因子和趋化因子，包括调节性细胞因子如IL2、IL23a和IL12b。此外，我们证明NFATc2结合是诱导组蛋白3赖氨酸4三甲基化（H3K4me3）表观遗传标记所必需的，该标记与基因表达增强相关。总之，这些数据表明转录因子NFATc2介导DC细胞因子和趋化因子基因的表观遗传修饰，导致其表达激活。
