title: The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus.
abstract: The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (MHC I)-restricted thymocytes, but not for other events associated with their positive selection, including the initiation of cytotoxic gene expression, corticomedullary migration, or thymus exit. We further show that Ets1 promotes expression of Runx3, a transcription factor important for CD8 T cell differentiation and the cessation of Cd4 gene expression. Enforced Runx3 expression in Ets1-deficient MHC I-restricted thymocytes largely rescued their impaired Cd4 silencing, indicating that Ets1 is not required for Runx3 function. Finally, we document that Ets1 binds at least two evolutionarily conserved regions within the Runx3 gene in vivo, supporting the possibility that Ets1 directly contributes to Runx3 transcription. These findings identify Ets1 as a key player during CD8 lineage differentiation and indicate that it acts, at least in part, by promoting Runx3 expression.
authors.affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Zamisch
authors.forename: Linhua
authors.initials: L
authors.lastname: Tian
authors.forename: Roland
authors.initials: R
authors.lastname: Grenningloh
authors.forename: Yumei
authors.initials: Y
authors.lastname: Xiong
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: Wildt
authors.forename: Marc
authors.initials: M
authors.lastname: Ehlers
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Ho
authors.forename: Rémy
authors.initials: R
authors.lastname: Bosselut
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000276:immunology*; D020218:Response Elements / Q000235:genetics / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D050677:Core Binding Factor Alpha 3 Subunit; C494042:Ets1 protein, mouse; D015395:Histocompatibility Antigens Class I; D050784:Proto-Oncogene Protein c-ets-1; C493730:Runx3 protein, mouse