Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins

Sp1-like transcription factors are characterized by three highly homologous C-terminal zinc finger motifs that bind CC-rich sequences. These proteins behave as either activators or repressors and have begun to be classified i nto different subfamilies based upon the presence of conserved motifs outsi de the zinc finger domain. This classification predicts that different Sp1- like subfamilies share certain functional properties. TIEG1 and TIEG2 const itute a new subfamily of transforming growth factor-beta-inducible Sp1-like proteins whose zinc finger motifs also bind GC-rich sequences. However, re gions outside of the DNA-binding domain that differ in structure from other Sp1-like family members remain poorly characterized. Here, we have used ex tensive mutagenesis and GAL4-based transcriptional assays to identify three repression domains within TIEG1 and TIEG2 that we call R1, R2, and R3. R1 is 10 amino acids, R2 is 12 amino acids, and R3 is approximately 80 amino a cids long None of these domains share homology with previously described tr anscriptional regulatory motifs, but they share strong sequence homology an d are functionally conserved between TIEG1 and TIEG2. Together, these data demonstrate that TIEG proteins are capable of repressing transcription, def ine domains critical for this function, and further support the idea that d ifferent subfamilies of Sp1-like proteins have evolved to mediate distinct transcriptional functions.