Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-ε and T cell receptor α enhancers

M. Oosterwegel, M. Van de Wetering, D. Dooijes, L. Klomp, A. Winoto, K. Georgopoulos, F. Meijlink, H. Clevers

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131 Citaten (Scopus)

Samenvatting

CD3-ε gene expression is confined to the T cell lineage. We have recently identified and cloned a human transcription factor, TCF-1, that binds to a functional element in the T lymphocyte-specific enhancer of CD3-ε. In a panel of human cell lines, TCF-1 expression was restricted to T lineage cells. TCF-1 belonged to a novel family of genes that contain the so-called high mobility group 1 (HMG) box. Here we report the cloning of murine TCF-1. Two splice alternatives were identified that were not previously observed in human TCF-1. Murine and human TCF-1 displayed a 95.5% overall amino acid homology. Recombinant murine and human TCF-1 recognized the same sequence motif in the CD3-ε enhancer as judged by gel retardation and methylation interference assays. With the murine cDNA clones several aspects of TCF-1 were analyzed. First, deletion analysis revealed that a region of TCF-1 containing the HMG box was sufficient for sequence-specific binding. Second, by high stringency Northern blotting and in situ hybridization, TCF-1 expression was shown to be confined to the thymus and to the T cell areas of the spleen. Third, TCF-1 bound specifically to a functional T cell-specific element in the T cell receptor α (TCR-α) enhancer. The T lineage-specific expression and the affinity for functional motifs in the TCR-α and CD3-ε enhancers imply an important role for TCF-1 in the establishment of the mature T cell phenotype.

Originele taal-2Engels
Pagina's (van-tot)1133-1142
Aantal pagina's10
TijdschriftJournal of Experimental Medicine
Volume173
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - 1991
Extern gepubliceerdJa

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