Identification and Characterization of YY1 and PIAS1 that Modulate CP2-mediated Transcriptional Activity

초록

Although CP2 is a ubiquitous transcription factor expressed in most of tissue, it also involves in the tissue-specific or stage-specific transcriptional activation of target genes, such as globin genes in red blood cells. It suggests that this specificity is regulated by interactions with other cellular partner proteins or by specific modifications of the CP2 protein. To identify the factors that modulate CP2 activity or directly participate in CP2-mediated transcriptional activation, we screened a phage display library and isolated a bunch of CP2 binding peptides. Through searching protein databases, we identified several putative CP2-binding proteins, including YY1 that was already known to interact with CP2 and a protein inhibitor of activated STAT1 (PIAS1). After cloning candidate genes, effects of PIAS1 and YY1 on the transcriptional modulation of CP2 activity were analyzed using reporter constructs containing CP2 binding sites in the mouse ?-globin gene promoter as a model in K562 and 293T cells. Indeed, PIAS1 increased the transcriptional activity of CP2, whereas YY1 suppressed the activity. Our results suggest that transcriptional activity of CP2 is regulated by several multifunctional protein-protein interactions, providing new insights on the regulatory mechanism of CP2 during development and differentiation.