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The TCR Locus Control Region Specifies Thymic, But Not Peripheral, Patterns of TCR Gene Expression¹

Department of Biological Sciences, City University of New York, Hunter College, New York, NY 10021

The molecular mechanisms ensuring the ordered expression of TCR genes are critical for proper T cell development. The mouse TCR -chain gene locus contains a cis-acting locus control region (LCR) that has been shown to direct integration site-independent, lymphoid organ-specific expression of transgenes in vivo. However, the fine cell type specificity and developmental timing of TCR LCR activity are both still unknown. To address these questions, we established a transgenic reporter model of TCR LCR function that allows for analysis of LCR activity in individual cells by the use of flow cytometry. In this study we report the activation of TCR LCR activity at the CD4^–CD8^–CD25^–CD44^– stage of thymocyte development that coincides with the onset of endogenous TCR gene rearrangement and expression. Surprisingly, TCR LCR activity appears to decrease in peripheral T cells where TCR mRNA is normally up-regulated. Furthermore, LCR-linked transgene activity is evident in T cells and B cells. These data show that the LCR has all the elements required to reliably reproduce a developmentally correct TCR-like expression pattern during thymic development and unexpectedly indicate that separate gene regulatory mechanisms are acting on the TCR gene in peripheral T cells to ensure its high level and fine cell type-specific expression.

This article has been cited by other articles:

				J. Gomos-Klein, F. Harrow, J. Alarcon, and B. D. Ortiz CTCF-Independent, but Not CTCF-Dependent, Elements Significantly Contribute to TCR-{alpha} Locus Control Region Activity J. Immunol., July 15, 2007; 179(2): 1088 - 1095. [Abstract] [Full Text] [PDF]