Cloning of GT Box-Binding Proteins: A Novel Spl Multigene Family Regulating T-Cell Receptor Gene Expression

Abstract

Analysis of a T-cell antigen receptor (TCR) α promoter from a variable gene segment (V) revealed a critical GT box element which is also found in upstream regions of several Vα genes, TCR enhancer, and regulatory elements of other genes. This element is necessary for TCR gene expression and binds several proteins. These GT box-binding proteins were identified as members of a novel Spl multigene family. Two of them, which we term Sp2 and Sp3, were cloned. Sp2 and Sp3 contain zinc fingers and transactivation domains similar to those of Spl. Like Spl, Sp2 and Sp3 are expressed ubiquitously, and their in vitro-translated products bind to the GT box in TCR Vα promoters. Sp3, in particular, also binds to the Spl consensus sequence GC box and has binding activity similar to that of Spl. As the GT box has also previously been shown to play a role in gene regulation of other genes, these newly isolated Sp2 and Sp3 proteins might regulate expression not only of the TCR gene but of other genes as well.