The LIM protein FHL3 binds basic Kruppel-like factor/Kruppel-like factor 3 and its co-repressor C-terminal-binding protein 2

The ability of DNA-binding transcription factors to recruit specific cofactors is central to the mechanism by which they regulate gene expression. BKLF/KLF3, a member of the Kruppel-like factor family of zinc finger proteins, is a potent transcriptional repressor that recruits a CtBP co-repressor. We show here that BKLF also recruits the four and a half LIM domain protein FHL3. Different but closely linked regions of BKLF mediate contact with CtBP2 and FHL3. We present evidence that CtBP2 also interacts with FHL3 and demonstrate that the three proteins co-elute in gel filtration experiments. CtBP and FHL proteins have been implicated in both nuclear and cytoplasmic functions, but expression of BKLF promotes the nuclear accumulation of both FHL3 and CtBP2. FHL proteins have been shown to act predominantly as co-activators of transcription. However, we find FHL3 can repress transcription. We suggest that LIM proteins like FHL3 are important in assembling specific repression or activation complexes, depending on conditions such as cofactor availability and promoter context.