Figure 6.
The interaction between CtBP and KLF8 is negatively regulated by PCAF and p300 mediated acetylation. (A) PCAF, p300, or HDAC inhibitors inhibit KLF8 interaction with CtBP. HEK293 cells were co-transfected with expression vectors coding for HA-KLF8, PCAF, or p300 or treated with HDAC inhibitors (trichostatin A, sodium butyrate, and nicotinamide) as indicated. Endogenous CtBP was immunoprecipi-tated (IP) using an anti-CtBP antibody, and blotted (IB) with either anti-HA (panel a), or anti-CtBP antibodies (panel b). Conversely, KLF8 was immunopre-cipitated using anti-HA, and blotted using anti-CtBP (panel c) or anti-HA antibodies (panel d). (B) Alignment of KLF8 orthologs shows that the PVDLS motif and lysines 93 and 95 are highly conserved. (C & D), Acetylation at lysines 93 and 95 inhibits KLF8 interaction with CtBP. Experiments were performed similarly as in A except that K93R or K93Q (C) or K95R or K95Q (D) was transfected. Shown are representative experiments where n=3. Expression of the transfected constructs was verified by whole cell lysate blotting (data not shown).