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Promoter During Immature T Cell Development1
Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba, Japan
The pre-TCR
(pT) is exclusively expressed in immature
thymocytes and constitutes the pre-TCR complex with TCR
, which
regulates early T cell differentiation. Despite the recent
identification of the pT enhancer, the contribution of the promoter
region, the direct DNA-protein interaction, and the regulation of such
interaction along with T cell development have not been investigated.
We analyzed the pT promoter region and identified the critical
elements for transcription of the pT gene. The pT promoter was
found to contain two consecutive E-box elements that are critical for
pT transcription. The E-box elements in the promoter region formed
the specific DNA-protein complex that was exclusively observed in
immature thymocytes, not in mature thymocytes and T cells. The E
proteins in this complex were identified as E2A and HeLa E-box binding
protein (HEB), and overexpression of E2A and HEB resulted in activation
of the pT promoter. The binding complex in the consecutive E-boxes
in the pT promoter changed along with T cell development, as a
distinct DNA-binding complex was observed in mature T cells. Comparing
the E-box regions in the enhancer and the promoter, those in the
promoter appear to make a greater contribution to pT gene
transcription.
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