Human Kruppel-like Factor 8: A CACCC-box binding protein that associates with CtBP and represses transcription

Abstract

CACCC-boxes are recognised by transcription factors of the Sp/Kruppel-like Factor (Sp1/KLF) family. Here we describe one member of this family, KLF8/ZNF741/ BKLF3 (KLF8). KLF8 contains a characteristic C-terminal DNA-binding domain comprised of three Kruppel-like zinc fingers, but also has limited homology to another family member, KLF3/Basic Kruppel-like Factor (KLF3/ BKLF), in its N-terminus. Most significantly, it shares with KLF3/BKLF a Pro-Val-Asp-Leu-Ser/Thr motif. In KLF3/BKLF this motif mediates contact with the co-repressor protein C-terminal Binding Protein (CtBP). We demonstrate that the KLF8 Pro-Val-Asp-Leu-Ser motif also contacts CtBP. We show that the N-terminus of KLF8 functions as a repression domain and that its activity relies on the integrity of the CtBP recognition motif. We demonstrate that the zinc fingers of KLF8 recognize CACCC elements in DNA and that full-length KLF8 can repress a CACCC-dependent promoter. Finally we determine that KLF8 is broadly expressed in human tissues. These results establish KLF8 as a CACCC-box binding protein that associates with CtBP and represses transcription.