The Journal of Experimental Medicine
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Published 6 December 2004. doi:10.1084/jem.20041041
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 11, 1427-1435
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Dynamic Repositioning of CD4 and CD8 Genes during T Cell Development

Stephanie Delaire, Yina Hsing Huang, Shaio Wei Chan, and Ellen A. Robey

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720

Address correspondence to Ellen A. Robey, Dept. of Molecular and Cell Biology, 475 Life Science Additions, University of California, Berkeley, Berkeley, CA 94720. Phone: (510) 642-8669; Fax: (510) 643-9500; email: erobey{at}uclink.berkeley.edu

Although stable repression of CD4 and CD8 genes is a central feature of T cell lineage commitment, we lack detailed information about the timing and mechanism of this repression. Stable gene repression has been linked to the position of genes within the nucleus. Therefore, information about the nuclear position of CD4 and CD8 genes during T cell development could provide insights into both the mechanism of regulation of CD4 and CD8 genes, and the process of lineage commitment. Here, we report that lineage-specific repression of CD4 and CD8 genes is associated with the repositioning of alleles close to heterochromatin. We also provide evidence that the relocalization of CD4 and CD8 genes to heterochromatin can occur as an early response to positive selection signals. We discuss our results in terms of our current knowledge of CD4 and CD8 gene regulation and CD4 versus CD8 lineage commitment.

Key Words: lineage commitment • heterochromatin • positive selection • gene repression • nuclear position

S. Delaire and Y.H. Huang contributed equally to this work.

Y.H. Huang's present address is Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA 92121.

Abbreviations used in this paper: DN, double negative; DP, double positive; FISH, fluorescence in situ hybridization; SP, single positive.


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