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.