Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J

Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion 71110, Crete, Greece. kretsova@imbb.forth.gr.

We show here that steroid receptor coactivator 1 (SRC-1) is a coactivator of MHC class II genes that stimulates their interferon gamma (IFNgamma) 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 IFNgamma stimulation. Most importantly, SRC-1 relieves the inhibitory action of estrogens on the IFNgamma-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.

Mesh Terms:
Animals, Base Sequence, Breast Neoplasms, COS Cells, Cell Line, Tumor, Cercopithecus aethiops, DNA Primers, Genes, MHC Class II, Genes, Reporter, Hela Cells, Histocompatibility Antigens Class II, Histone Acetyltransferases, Humans, Interferon-gamma, Luciferases, Mice, Nuclear Receptor Coactivator 1, Polymerase Chain Reaction, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Steroids, Transcription Factors, Transfection

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