Down-regulation of the SWI/SNF chromatin remodeling activity by TCR signaling is required for proper thymocyte maturation.
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.
Lee
Kyoo Y
KY
Department of Biological Sciences, Institute of Molecular Biology and Genetics, and Research Center for Functional Cellulomics, Seoul National University, Seoul, Korea.
Choi
Young I
YI
Kim
Jieun
J
Choi
Jin W
JW
Sohn
Dong H
DH
Lee
Changjin
C
Jeon
Sung H
SH
Seong
Rho H
RH
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors* / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000502:physiology
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006131:Growth Inhibitors; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D015534:Trans-Activators; D014157:Transcription Factors