Steroid Receptor Coactivator 1 Links the Steroid and Interferon γ Response Pathways

Abstract

Abstract We show here that steroid receptor coactivator 1 (SRC-1) is a coactivator of MHC class II genes that stimulates their interferon γ (IFNγ) and class II transactivator (CIITA)-mediated expression. SRC-1 interacts physically with the N-terminal activation domain of CIITA through two regions: one central [extending from amino acids (aa) 360–839] that contains the nuclear receptors binding region and one C-terminal (aa 1138–1441) that contains the activation domain 2. Using chromatin immunoprecipitation assays we show that SRC-1 recruitment on the class II promoter is enhanced upon IFNγ stimulation. Most importantly, SRC-1 relieves the inhibitory action of estrogens on the IFNγ-mediated induction of class II genes in transient transfection assays. We provide evidence that inhibition by estradiol is due to multiple events such as slightly reduced recruitment of CIITA and SRC-1 and severely inhibited assembly of the preinitiation complex.