Acetylation of steroidogenic factor 1 protein regulates its transcriptional activity and recruits the coactivator GCN5

Steroidogenic factor-1 (SF-1) is an orphan nuclear receptor that plays an e ssential role in the development of the hypothalamic-pituitary-gonadal axis in both sexes. SF-1 belongs to the hormone nuclear receptor superfamily an d possesses an N-terminal DNA binding domain and a C-terminal ligand bindin g domain. Activation function domain 2 is located C-terminal of the ligand binding domain of SF-1 and is important for the transactivation of target g enes. Coactivators with histone acetyltransferase activity such as cAMP res ponse element-binding protein-binding protein and steroid receptor coactiva tor 1 interact and increase SF-1-mediated transcriptional activity. In this study we demonstrate that SF-1 is acetylated in vivo. Histone acetyltransf erase GCN5 acetylates SF-1 in vitro. Moreover, we found that SF-1 recruited a novel coactivator GCN5, which can be a newly identified coactivator for SF-1. Acetylation of SF-1 stimulates its transcriptional activity. Inhibiti on of deacetylation by trichostatin A, a histone deacetylase inhibitor, inc reased SF-1-mediated transactivation and stabilized and induced the nuclear export of the SF-1 protein.