Identification and characterization of a transcriptional regulator for thelck proximal promoter

The lck gene encodes a protein-tyrosine kinase that plays a key role in sig naling mediated through T cell receptor (TCR) and pre-TCR complexes. Transc ription of the lck gene is regulated by two independent promoter elements: the proximal and distal promoters. Previous studies employing transgenic mi ce demonstrated that the sequence between -584 and -240 from the transcript ion start site in the mouse lck proximal promoter is required for its tissu e-specific expression in the thymus, In this study, we demonstrate that a K ruppel-like zinc finger protein, mt beta (BFCOL1, BERF-1, ZBP-89, ZNF148), previously cloned as a protein that binds to the CD3 delta gene enhancer, b inds to the -365 to -328 region of the lck proximal promoter. mt beta is ub iquitously expressed in various cell lines and mouse tissues. Overexpressed mt beta is more active in T-lineage cells than B-lineage cells for transac tivating an artificial promoter consisting of the mt beta binding site and a TATA box. Activity of the lck proximal promoter was significantly impaire d by mutating the mt beta binding site or by reducing mt beta protein expre ssion level by using antisense mRNA. Our results indicate that mt beta acti vity is regulated in a tissue-specific manner and that mt beta is a critica l transactivator for the lck proximal promoter.