TRANSCRIPTIONAL ACTIVATION OF THE HUMAN T-LYMPHOTROPIC VIRUS TYPE-I LONG TERMINAL REPEAT BY FUNCTIONAL INTERACTION OF TAX(1) AND ETS1

Transcription regulation of the oncogenic retrovirus human T-lymphotro pic virus type I (HTLV-I) involves the composite activity of both vira l and cellular transcription factors. The HTLV-I transforming protein, Tax1, modulates the activity of several cellular transcription factor s, upregulating the level of viral gene expression. In addition, cellu lar transcription factors, such as Ets1, independently bind to the vir al long terminal repeat in a sequence-specific manner and activate tra nscription. It was of interest to analyze the possible interaction of Tax1 and Ets1 in viral gene regulation. We now report that Tax1 and Et s1 increase expression from the HTLV-1 promoter in a cooperative manne r. The level of expression was increased 5- to 10-fold above the combi ned individual effect of Tax1 and Ets1. S1 nuclease analysis demonstra ted that the cooperative effect was due to an increase in the levels o f steady-state RNA. The functional interaction between Tax1 and Ets1 r equired the presence of the Tax1-responsive 21-bp repeat element TRE-1 and the Ets1-responsive element ERR-1. These results suggested the po ssible interaction of Ets1 with transcriptional regulatory proteins th at bind to the 21-bp repeats. This interaction is demonstrated by decr eased electrophoretic mobility of specific 21-bp repeat gel shift comp lexes in the presence of Ets1. Furthermore, interaction of Ets1 with t he 21-bp repeat-binding proteins enhances the relative efficiency of b inding to the DNA. This cooperative interaction between Ets1 and prote ins which bind to the Tax1-responsive 21-bp repeats suggests a possibl e role for Ets1 in the regulation of viral gene expression.