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Down-regulation of the SWI/SNF chromatin remodeling activity by TCR signaling is required for proper thymocyte maturation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Jun 01; Vol. 178 (11), pp. 7088-96. - Publication Year :
- 2007
-
Abstract
- The process of thymocyte development requires an exquisite regulation of many genes via transcription factors and chromatin remodeling activities. Even though the SWI/SNF chromatin remodeling complex has been thought to play important roles during thymocyte development, its known function is very limited. In this study, we show that the SWI/SNF chromatin remodeling activity is finely regulated during thymocyte maturation process, especially during thymocyte selections. We found that TCR signaling directly down-regulates mBRG1 and SWI3-related gene, the core components of murine SWI/SNF complex, during thymocyte maturation. Constitutive expression of SWI3-related gene in developing thymocytes attenuated the down-regulation of the SWI/SNF complex and resulted in a change in the expression of genes such as linker for activation of T cells and casitas B lineage lymphoma, which affected the TCR-mediated intracellular signaling pathway. The defects in TCR signaling resulted in the disruption of both positive and negative selections in specific TCR transgenic mice systems. Our results state, for the first time, that the chromatin remodeling activity needs to be finely controlled for proper thymocyte selection and maturation processes.
- Subjects :
- Animals
Cell Differentiation genetics
Cells, Cultured
Chromatin genetics
Chromosomal Proteins, Non-Histone physiology
Down-Regulation genetics
Female
Growth Inhibitors antagonists & inhibitors
Growth Inhibitors biosynthesis
Growth Inhibitors genetics
Male
Mice
Mice, Inbred A
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Receptors, Antigen, T-Cell antagonists & inhibitors
Receptors, Antigen, T-Cell genetics
Repressor Proteins antagonists & inhibitors
Repressor Proteins biosynthesis
Repressor Proteins genetics
Signal Transduction genetics
T-Lymphocyte Subsets cytology
T-Lymphocyte Subsets metabolism
Thymus Gland cytology
Thymus Gland metabolism
Trans-Activators antagonists & inhibitors
Trans-Activators biosynthesis
Trans-Activators genetics
Transcription Factors physiology
Cell Differentiation immunology
Chromatin metabolism
Chromosomal Proteins, Non-Histone antagonists & inhibitors
Down-Regulation immunology
Receptors, Antigen, T-Cell physiology
Signal Transduction immunology
T-Lymphocyte Subsets immunology
Thymus Gland immunology
Transcription Factors antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 178
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17513758
- Full Text :
- https://doi.org/10.4049/jimmunol.178.11.7088