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Submitted on December 23, 2002
Accepted on August 15, 2003
response pathways
1 Department of Biology, University of Crete, Heraklion 71110, Crete, Greece; Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology, Heraklion 71110, Crete, Greece
* To whom correspondence should be addressed. E-mail: kretsova{at}imbb.forth.gr.
We show here that SRC-1 is a coactivator of MHC class II genes that stimulates their interferon 
(IFN) and CIITA mediated expression. SRC-1 interacts physically with the N-terminal activation domain of CIITA through two regions: one central (extending from 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 IFN stimulation. Most importantly, SRC-1 relieves the inhibitory action of estrogens on the IFN 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 Pre-Initiation Complex.
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