title: NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation.
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.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore yu_hong_bing@immunol.a-star.edu.sg.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Yu
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
authors.forename: Marina
authors.initials: M
authors.lastname: Yurieva
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
authors.forename: Akhila
authors.initials: A
authors.lastname: Balachander
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
authors.forename: Ivy
authors.initials: I
authors.lastname: Foo
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Leong
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
authors.forename: Teresa
authors.initials: T
authors.lastname: Zelante
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*Star), Biopolis, Singapore paola.castagnoli@gmail.com.
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000378:metabolism*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D000099181:Dectin-1
chemical_list: D018925:Chemokines; D016207:Cytokines; D006657:Histones; D037181:Lectins, C-Type; D050778:NFATC Transcription Factors; D000099181:Dectin-1