Abstract
The regulation of gene repression by corepressors is a controlled process. Surface-enhanced laser desorption ionization MS proteomic analysis and a yeast two-hybrid screen showed independently that the corepressor Alien interacts with the CREB-binding protein (CBP) coactivator. This interaction was further confirmed by coimmunoprecipitation and glutathione S-transferase pull-down experiments, suggesting that Alien interacts invivo and invitro with the histone acetyltransferase (HAT) coactivators CBP and its paralog p300. Acetylation detection experiments indicated that Alien is acetylated invivo. Furthermore, Alien interacts with the central region of CBP/p300 containing the HAT domain and becomes acetylated invitro. When an inhibitor of CBP/p300 HAT activity was employed, the Alien-mediated silencing was enhanced. Thus, these findings suggest crosstalk between corepressors and coactivators, and indicate fine-tuning of corepressor function by post-translational modification through corepressor acetylation.