REV-ERBα deficiency alters the epigenetic landscape and differentially affects clock gene expression in ILC3 subsets. REV-ERBα deficiency alters the epigenetic.

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REV-ERBα deficiency alters the epigenetic landscape and differentially affects clock gene expression in ILC3 subsets. REV-ERBα deficiency alters the epigenetic landscape and differentially affects clock gene expression in ILC3 subsets. (A) Transcription factor motifs enriched in regions that are differentially accessible in Nr1d1−/– NKp46− (DN and CCR6+) ILC3s versus Nr1d1+/+ NKp46− ILC3s; log P values for enrichment and frequency of target sequences with motif. Circadian-related motifs shown in bold; #, not significant or possible false-positive result. (B) Gene expressions of sorted NKp46+ and CCR6+ ILC3s from Nr1d1+/+ and Nr1d1−/− siLP by RT-qPCR, relative expression to Actb. (C and D) UCSC Genome Browser view of ATAC-seq tracks of mouse (C) Nfil3, (D) Il17, and Tbp loci in the indicated ILC3 subsets. Black bars on top represent locations of RORγt binding sites based on published RORγt chromatin immunoprecipitation sequencing in TH17 cells (GEO: GSE56020). The differential tracks are subtraction plots showing differences in peak accessibility between Nr1d1+/+ and Nr1d1−/− ILC3s. (E) Volcano plot of genes with >1.5-fold differential expression (red) in Nr1d1+/+ versus Nr1d1−/− CCR6+ ILC3s (left); heatmap of known RORγt target genes differentially expressed in Nr1d1+/+ and Nr1d1−/− CCR6+ ILC3s. Statistical analysis was performed using one-way ANOVA with multiple comparisons test (B). Bars indicate means (±SD). ns, not significant; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Data are representative of at least two independent experiments (n = 3 per group per experiment) (B). Qianli Wang et al. Sci. Immunol. 2019;4:eaay7501 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works