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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 3017-3025
Promoter Element for Transcription of Unrearranged T-Cell Receptor
 -Chain Gene in Pro-T Cells
Raymond T. Doty,
Dong Xia,
Suzanne P. Nguyen,
Tanya R. Hathaway, and
Dennis M. Willerford
From the Departments of Medicine and Immunology, University of
Washington, Puget Sound Blood Center, Seattle.
The hallmark of T- and B-lymphocyte development is the rearrangement
of variable (V), diversity (D), and joining (J) segments of T-cell
receptor (TCR) and immunoglobulin (Ig) genes to generate a diverse
repertoire of antigen receptor specificities in the immune system. The
process of V(D)J recombination is shared in the rearrangement of all
seven antigen receptor genes and is controlled by changes in chromatin
structure, which regulate accessibility to the recombinase apparatus in
a lineage- and stage-specific manner. These chromatin changes are
linked to transcription of the locus in its unrearranged (germline)
configuration. To understand how germline transcription of the
TCR -chain gene is regulated, we determined the structure of germline
transcripts initiating near the D1 segment and identified a promoter
within this region. The D1 promoter is active in the presence of the
TCR enhancer (E), and in this context, exhibits preferential
activity in pro-T versus mature T-cell lines, as well as T- versus
B-lineage specificity. These studies provide insight into the
developmental regulation of TCR germline transcription, one of the
earliest steps in T-cell differentiation.
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