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 GC-rich sequences. These proteins behave as either activators or repressors and have begun to be classified into different subfamilies based upon the presence of conserved motifs outside the zinc finger domain. This classification predicts that different Sp1-like subfamilies share certain functional properties. TIEG1 and TIEG2 constitute a new subfamily of transforming growth factor-beta-inducible Sp1-like proteins whose zinc finger motifs also bind GC-rich sequences. However, regions outside of the DNA-binding domain that differ in structure from other Sp1-like family members remain poorly characterized. Here, we have used extensive 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 acids long. None of these domains share homology with previously described transcriptional regulatory motifs, but they share strong sequence homology and are functionally conserved between TIEG1 and TIEG2. Together, these data demonstrate that TIEG proteins are capable of repressing transcription, define domains critical for this function, and further support the idea that different subfamilies of Sp1-like proteins have evolved to mediate distinct transcriptional functions.
Cook
T
T
Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55901, USA.
Gebelein
B
B
Belal
M
M
Mesa
K
K
Urrutia
R
R
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002874:Chromosome Mapping; D017124:Conserved Sequence; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D020868:Gene Silencing; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D012097:Repressor Proteins / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D016329:Sp1 Transcription Factor / Q000737:chemistry* / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors