title: Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy.
abstract: T cell anergy is one of the mechanisms contributing to peripheral tolerance, particularly in the context of progressively growing tumors and in tolerogenic treatments promoting allograft acceptance. We recently reported that early growth response gene 2 (Egr2) is a critical transcription factor for the induction of anergy in vitro and in vivo, which was identified based on its ability to regulate the expression of inhibitory signaling molecules diacylglycerol kinase (DGK)-α and -ζ. We reasoned that other transcriptional targets of Egr2 might encode additional factors important for T cell anergy and immune regulation. Thus, we conducted two sets of genome-wide screens: gene expression profiling of wild type versus Egr2-deleted T cells treated under anergizing conditions, and a ChIP-Seq analysis to identify genes that bind Egr2 in anergic cells. Merging of these data sets revealed 49 targets that are directly regulated by Egr2. Among these are inhibitory signaling molecules previously reported to contribute to T cell anergy, but unexpectedly, also cell surface molecules and secreted factors, including lymphocyte-activation gene 3 (Lag3), Class-I-MHC-restricted T cell associated molecule (Crtam), Semaphorin 7A (Sema7A), and chemokine CCL1. These observations suggest that anergic T cells might not simply be functionally inert, and may have additional functional properties oriented towards other cellular components of the immune system.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zha
authors.forename: Robbert M
authors.initials: RM
authors.lastname: Spaapen
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mathew
authors.forename: Kenneth
authors.initials: K
authors.lastname: Barr
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017635:Clonal Anergy / Q000235:genetics*; D051767:Early Growth Response Protein 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D018390:Gene Targeting; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse
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