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CRTAM is negatively regulated by ZEB1 in T cells
C Rojas-Marquez1, R Valle-Rios2, E Lopez-Bayghen3
1Departamento 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.
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.
Insights
Zinc finger E-box-binding protein (ZEB1) represses the Class-I MHC-restricted T cell associated molecule (CRTAM) gene. This regulation by ZEB1 impacts T cell activation and adaptive immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Gene Regulation
Background:
- T cell activation induces genes crucial for immune responses.
- Class-I MHC-restricted T cell associated molecule (CRTAM) is vital for T cell development, proliferation, and polarity.
- AP-1 family members regulate CRTAM expression during antigenic activation.
Purpose of the Study:
- To investigate the role of zinc finger E-box-binding protein (ZEB1) as a regulator of CRTAM expression.
- To elucidate the mechanism by which ZEB1 affects CRTAM gene transcription.
Main Methods:
- Reporter assays to measure CRTAM promoter activity.
- Analysis of endogenous CRTAM levels in human T cells.
- Site-directed mutagenesis of E-box-like elements in the CRTAM promoter.
Main Results:
- Overexpression of ZEB1 significantly repressed CRTAM promoter activity.
- ZEB1 overexpression led to decreased endogenous CRTAM levels in human T cells.
- Mutation of E-box-like elements abolished ZEB1-mediated transcriptional repression of CRTAM.
Conclusions:
- ZEB1 acts as a transcriptional repressor of the CRTAM gene.
- ZEB1 modulates CRTAM expression in both resting and activated T cells.
- ZEB1-mediated repression of CRTAM influences adaptive immune responses.
