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Nucleic Acids Res. 2015 Jan;43(2):836-47. doi: 10.1093/nar/gku1369. Epub 2014 Dec 30.

NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation.

Author information

1
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore yu_hong_bing@immunol.a-star.edu.sg.
2
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
3
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore paola.castagnoli@gmail.com.

Abstract

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.

PMID:
25550437
PMCID:
PMC4333412
DOI:
10.1093/nar/gku1369
[Indexed for MEDLINE]
Free PMC Article

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