title: CRTAM is negatively regulated by ZEB1 in T cells.
abstract: T cell activation leads to the induction of genes that are required for appropriate immune responses. This includes CRTAM (Class-I MHC-restricted T cell associated molecule), a protein that plays a key role in T cell development, proliferation, and generating cell polarity during activation. We previously characterized the CRTAM promoter and described how AP-1 family members are important for inducing CRTAM expression upon antigenic activation. Here, we show that CRTAM is a molecular target for ZEB1 (zinc finger E-box-binding protein), a homeodomain/Zn finger transcription factor. Overexpression of ZEB1 repressed CRTAM promoter activity, as well as endogenous CRTAM levels in human T cells. ZEB1-mediated transcriptional repression was abolished when E-box-like elements in the CRTAM promoter are mutated. In summary, ZEB1 functions as a transcriptional repressor for the CRTAM gene in both non-stimulated and stimulated T cells, thereby modulating adaptive immune responses.
authors.affiliation: Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV)-IPN, Av. IPN No. 2508, Colonia San Pedro Zacatenco, México, DF, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Rojas-Marquez
authors.affiliation: Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Fedérico Gómez, México, DF, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Valle-Rios
authors.affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados (CINVESTAV)-IPN, Av. IPN No. 2508, Colonia San Pedro Zacatenco, México, DF, Mexico. Electronic address: ebayghen@cinvestav.mx.
authors.forename: E
authors.initials: E
authors.lastname: Lopez-Bayghen
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV)-IPN, Av. IPN No. 2508, Colonia San Pedro Zacatenco, México, DF, Mexico. Electronic address: vortiz@cinvestav.mx.
authors.forename: V
authors.initials: V
authors.lastname: Ortiz-Navarrete
mesh_terms: D056704:Adaptive Immunity; D001665:Binding Sites; D005786:Gene Expression Regulation / Q000276:immunology*; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics* / Q000276:immunology; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D014158:Transcription, Genetic; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D007136:Immunoglobulins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C408522:class-I restricted T cell-associated molecule; D008156:Luciferases
keywords: CRTAM; E-box-like elements; Promoter; Repression; Transcription; ZEB1