POZ Domain Transcription Factor, FBI-1, Represses Transcription of ADH5/FDH by Interacting with the Zinc Finger and Interfering with DNA Binding Activity of Sp1

• Published in: The Journal of biological chemistry Vol. 277; no. 30; pp. 26761 - 26768
• Main Authors: Lee, Dong-Kee, Suh, Dongchul, Edenberg, Howard J., Hur, Man-Wook
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.07.2002; American Society for Biochemistry and Molecular Biology
• Subjects: Aldehyde Oxidoreductases - genetics; Aldehyde Oxidoreductases - metabolism; Amino Acid Sequence; Animals; Cell Nucleus - metabolism; Chromatin - metabolism; Deoxyribonuclease I - metabolism; DNA - metabolism; DNA-Binding Proteins - metabolism; Gene Library; HeLa Cells; Humans; Mice; Molecular Sequence Data; Multigene Family; Plasmids - metabolism; Polymerase Chain Reaction; Precipitin Tests; Promoter Regions, Genetic; Protein Binding; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Sp1 Transcription Factor - metabolism; Transcription Factors; Transcription, Genetic; Zinc Fingers
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M202078200

The POZ domain is a protein-protein interaction motif that is found in many transcription factors, which are important for development, oncogenesis, apoptosis, and transcription repression. We cloned the POZ domain transcription factor, FBI-1, that recognizes the cis-element (bp −38 to −22) located just upstream of the core Sp1 binding sites (bp −22 to +22) of theADH5/FDH minimal promoter (bp −38 to +61)in vitro and in vivo, as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. The ADH5/FDH minimal promoter is potently repressed by the FBI-1. Glutathione S-transferase fusion protein pull-down showed that the POZ domains of FBI-1, Plzf, and Bcl-6 directly interact with the zinc finger DNA binding domain of Sp1. DNase I footprinting assays showed that the interaction prevents binding of Sp1 to the GC boxes of the ADH5/FDHpromoter. Gal4-POZ domain fusions targeted proximal to the GC boxes repress transcription of the Gal4 upstream activator sequence-Sp1-adenovirus major late promoter. Our data suggest that POZ domain represses transcription by interacting with Sp1 zinc fingers and by interfering with the DNA binding activity of Sp1.