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 cel ls by the binding of cellular factors, called IBP-s, to the SV40 late promoter; repression is relieved after the onset of viral DNA replicat ion 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. Mer tz, Proc. Natl. Acad. Sci. USA 92:8586-8590, 1995). Here, we show that the thyroid hormone receptor TR alpha 1, in combination with retinoid X receptor alpha (RXR alpha), is specifically bound at the transcript ional initiation site of the major late promoter of SV40; This binding repressed transcription from the SV40. late promoter by preventing th e formation of pre-initiation complexes. Addition of the thyroid hormo ne 3,5,3'-L-triiodothyronine (T-3) resulted in reversal of this repres sion in cotransfected CV-1 cells. Interestingly, repression did not oc cur when this thyroid response element (TRE) was translocated to 50 bp upstream of the major late initiation site. Binding of TR alpha 1/RXR alpha heterodimers to this TRE induced bending of the promoter DNA. W e conclude that hormones and their receptors can directly affect the e xpression of SV40, probably by affecting protein-protein and protein-D NA interactions involved in the formation of functional preinitiation complexes.