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Down-Regulation of the SWI/SNF Chromatin Remodeling Activity by TCR Signaling Is Required for Proper Thymocyte Maturation¹

Kyoo Y. Lee^2,*, Young I. Choi^2,*, Jieun Kim^*, Jin W. Choi^*, Dong H. Sohn^*, Changjin Lee^*, Sung H. Jeon and Rho H. Seong^3,*

^* Department of Biological Sciences, Institute of Molecular Biology and Genetics, and Research Center for Functional Cellulomics, Seoul National University, Seoul, Korea; and Department of Life Science and Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Korea

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from Korea Science and Engineering Foundation, through Research Center for Functional Cellulomics (to R.H.S.). K.Y.L., Y.I.C., D.H.S., and J.W.C. were supported by BK21 Program from Ministry of Education and Human Resources Development. J.K. and J.W.C. were supported by Seoul Science Fellowship.

² K.Y.L. and Y.I.C. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Rho H. Seong, Department of Biological Sciences, Institute of Molecular Biology and Genetics (Building 105) and, Research Center for Functional Cellulomics, Seoul National University, Kwanak-gu Shinlim-dong, San 56-1, Korea. E-mail address: rhseong{at}snu.ac.kr

⁴ Abbreviations used in this paper: DP, double positive; Dex, dexamethasone; DN, double negative; GC, glucocorticoid; LAT, linker for activation of T cell; NLC, normal littermate control; PLC1, phospholipase C1; SP, single positive; SRG3, SWI3-related gene; UTR, untranslated region; Cbl, casitas B lineage lymphoma.