A NOVEL POU DOMAIN PROTEIN WHICH BINDS TO THE T-CELL RECEPTOR-BETA ENHANCER

POU domain proteins have been implicated in the regulation of a number of lineage-specific genes. Among the first POU domain proteins described were the immunoglobulin octamer-binding proteins Oct-I and Oct-2. It was therefore of special interest when we identified a novel lymphoid POU domain protein in Southwestern (DNA-protein) screens of T-cell lambdagt11 libraries. This novel POU protein, TCFbeta1, binds in a sequence-specific manner to a critical motif in the T-cell receptor (TCR) beta enhancer. Sequence analysis revealed that TCFbeta1 represents a new class of POU domain proteins which are distantly related to other POU proteins. TCFbeta1 is encoded by multiple exons whose organization is distinct from that of other POU domain proteins. The expression of TCFbeta, in a tissue-restricted manner and its ability to bind to multiple motifs in the TCR beta enhancer support a role in regulating TCR beta gene expression. The expression of TCFbeta1 in both B and T cells and the ability of recombinant TCFbeta1 to bind octamer and octamer-related motifs suggest that TCFbeta1 has additional roles in lymphoid cell function. The ability of TCFbeta1 to transactivate in a sequence-specific manner is consistent with a role for regulating lymphoid gene expression.