CLONING AND CHARACTERIZATION OF MCTBP2, A CO-REPRESSOR THAT ASSOCIATES WITH BASIC KRUPPEL-LIKE FACTOR AND OTHER MAMMALIAN TRANSCRIPTIONAL REGULATORS

Basic Kruppel-like factor (BKLF) is a zinc finger protein that recogni zes CACCC elements in DNA, It is expressed highly in erythroid tissues , the brain and other selected cell types. We have studied the activit y of BKLF and found that it is capable of repressing transcription, an d have mapped its repression domain to the N-terminus. We carried out a two-hybrid screen against BKLF and isolated a novel clone encoding m urine C-terminal-binding protein 2 (mCtBP2), mCtBP2 is related to huma n CtBP, a cellular protein which binds to a Pro-X-Asp-Leu-Ser motif in the C-terminus of the adenoviral oncoprotein, E1a. We show that mCtBP 2 recognizes a related motif in the minimal repression domain of BKLF, and the integrity of this motif is required for repression activity. Moreover, when tethered to a promoter by a heterologous DNA-binding do main, mCtBP2 functions as a potent repressor. Finally, we demonstrate that mCtBP2 also interacts with the mammalian transcripition factors E vi-1, AREB6, ZEE and FOG. These results establish a new member of the CtBP family, mCtBP2, as a mammalian co-repressor targeting diverse tra nscriptional regulators.