TRIM28 mediates chromatin modifications at the TCRα enhancer and regulates the development of T and natural killer T cells
| Autor: | Dapeng Zhou, Jiayi Yu, Florence Cammas, Xiaofei Zhou, Shao Cong Sun, Mikyoung Chang, Minying Zhang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Chromatin Immunoprecipitation
Receptors Antigen T-Cell alpha-beta Cellular differentiation T cell Immunoblotting Mice Transgenic Tripartite Motif-Containing Protein 28 Biology Histones Mice T-Lymphocyte Subsets medicine Animals Phosphorylation Homeodomain Proteins Thymocytes Multidisciplinary Nuclear Proteins Cell Differentiation Gene rearrangement Biological Sciences DNA Methylation Chromatin Assembly and Disassembly Flow Cytometry Natural killer T cell Molecular biology Chromatin Repressor Proteins Thymocyte Enhancer Elements Genetic medicine.anatomical_structure Natural Killer T-Cells Chromatin immunoprecipitation CD8 |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:20083-20088 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1214704109 |
| Popis: | T-cell receptor–α (TCRα) rearrangement in CD4 + CD8 + double-positive immature thymocytes is a prerequisite for production of αβ T cells and invariant natural killer T cells. This developmental event is regulated by the TCRα enhancer (Eα), which induces chromatin modification and recruitment of the recombination-activating proteins Rag1 and Rag2. However, the molecular mechanism underlying the activation and long-range action of Eα remains incompletely understood. We show here that the chromatin-modifying factor TRIM28 is highly expressed in double-positive thymocytes and persistently phosphorylated at serine 473. TRIM28 binds to Eα and induces histone 3 lysine 4 trimethylation in the Eα and distant regions of the TCRα locus, coupled with recruitment of Rag proteins. T-cell–conditional ablation of TRIM28 impaired TCRα gene rearrangement and compromised the development of αβ T cells and invariant natural killer T cells. These findings establish TRIM28 as a unique regulator of thymocyte development and highlight an epigenetic mechanism involving TRIM28-mediated active chromatin modification in the TCRα locus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|