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

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/Z NF741/ BKLF3 (KLF8), KLF8 contains a characteristic C-terminal DNA-binding domain comprised of three Kruppel-like zinc fingers, but also has limited h omology to another family member, KLF3/Basic Kruppel-like Factor (KLF3/ BKL F), in its N-terminus, Most significantly, it shares with KLF3/BKLF a Pro-V al-Asp-Leu-Ser/Thr motif, In KLF3/BKLF this motif mediates contact with the co-repressor protein C-terminal Binding Protein (CtBP), We demonstrate tha t 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 re lies on the integrity of the CtBP recognition motif. We demonstrate that th e zinc fingers of KLF8 recognize CACCC elements in DNA and that full-length KLF8 can repress a CACCC-dependent promoter. Finally we determine that KLF 8 is broadly expressed in human tissues. These results establish KLF8 as a CACCC-box binding protein that associates with CtBP and represses transcrip tion.