Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4

By M. Gilchrist, Vesteinn Thorsson, Bin Li, A. Rust, M. Korb, Kathleen A. Kennedy, Tsonwin Hai, H. Bolouri, Alan Aderem. Nature, 2006

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TAM receptors are pleiotropic inhibitors of the innate immune response. (2007, background): “We also examined mRNAs encoding six other negative regulators of TLR signaling—IRAK-M, SHIP, ATF-3, IRF-4, Triad3A, and Tollip (Liew et al., 2005; Negishi et al., 2005; Gilchrist et al., 2006).”
Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes (2018, background): “ID2 binds and represses basic helix-loop-helix transcription factors and has been linked to immune cell development and differentiation and ATF3 is a regulator of macrophage inflammatory state and cytokine signaling (Gilchrist et al., 2006).”
Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. (2016, background): “…by the repressors Atf3 and Irf2 (M3) are enriched in P1 (negatively regulated by M3); genes bound by Atf3 are also enriched in P4 (including IL-6) (Gilchrist et al., 2006); Stat3- and Rela- (M2) bound genes are enriched in P4, and Cebpb bound genes are enriched in P5 (both positively regulated by…”
Pattern recognition receptors and inflammation. (2010, methodology): “Using a systems biology approach, Aderem and colleagues identified ATF3 and C/EBPg as a suppressor and amplifier of TLR-mediated gene expression, respectively (Gilchrist et al., 2006; Litvak et al., 2009).”