Three mouse CP2 isoforms have distinct DNA binding and transcription activities and interact with each other to show unique regulatory profiles of the target gene expression

초록

CP2 is a transcription activator regulating various cellular promoters. We have isolated three mouse CP2 isoforms, namely CP2a, b, and c. CP2a and c showed about 75% homology, and CP2b contained additional 36 a.a in CP2a. To understand functional distinction among these isoforms, we analyzed their DNA binding and transcriptional activities. Whereas CP2a binds to consensus sequences with a half affinity of CP2c, CP2b could not bind at all. When CP2 isoforms were mixed, in combination, with probe DNA, CP2b abolished the binding capacity of CP2a or c. But, incubation of CP2a or c with DNA before CP2b addition could form DNA-protein complex. Activation domain of each isoform was mapped in the N-terminus and CP2b showed most strongest transcription activity. Overexpression of CP2a or b in K562 cells did not increased transcription of reporter containing CP2 binding sites while CP2c did in a dose dependent manner. Interestingly, CP2b showed strong synergy when cotransfected with CP2c, but not with CP2a. Thus, overall data suggest that the dynamic modulation of three CP2 isoforms is critical in target gene expression, regulating DNA binding, dimerization, and transcriptional activities.