Direct modulation of simian virus 40 late gene expression by thyroid hormone and its receptor

Transcription of the late genes of simian virus 40 (SV40) is repressed during the early phase of the lytic cycle of infection of primate cells by the binding of cellular factors, called IBP-s, to the SV40 late promoter; repression is relieved after the onset of viral DNA replication by titration of these repressors (S. R. Wiley, R. J. Kraus, F. R. Zuo, E. E. Murray, K. Loritz, and J. E. Mertz, Genes Dev. 7:2206-2219, 1993). Recently, we showed that IBP-s consists of several members of the steroid/thyroid hormone receptor superfamily (F. Zuo and J. E. Mertz, Proc. Natl. Acad. Sci. USA 92:8586-8590, 1995). Here, we show that the thyroid hormone receptor TRalpha1, in combination with retinoid X receptor alpha (RXRalpha), is specifically bound at the transcriptional initiation site of the major late promoter of SV40. This binding repressed transcription from the SV40 late promoter by preventing the formation of pre-initiation complexes. Addition of the thyroid hormone 3,5,3'-L-triiodothyronine (T3) resulted in reversal of this repression in cotransfected CV-1 cells. Interestingly, repression did not occur when this thyroid response element (TRE) was translocated to 50 bp upstream of the major late initiation site. Binding of TRalpha1/RXRalpha heterodimers to this TRE induced bending of the promoter DNA. We conclude that hormones and their receptors can directly affect the expression of SV40, probably by affecting protein-protein and protein-DNA interactions involved in the formation of functional preinitiation complexes.