Cloning of Murine TCF - 1 , a T Cell - specific Transcription Factor Interacting with Functional Motifs in the CD 3 - E and T Cell Receptor ct Enhancers

CD3-e 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-e . 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 ofmurine 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-e 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 a (TCRci) enhancer. The T lineage-specific expression and the affinity for functional motifs in the TCR-a and CD3-e enhancers imply an important role for TCF-1 in the establishment ofthe mature T cell phenotype .