Gene regulation mediated by interaction between HTLV-1 promoter elements and transcription factors tax and CREB

In this work we examine the role of three genetic control components in the regulation of HTLV-1 transcription: cyclic AMP-responsive element (CRE)-bi nding protein (CREB), the HTLV-1 trans-activator Tax, and the three Tax-res ponsive elements (TREs). We demonstrate that the in vivo efficiency of the HTLV-1 promoter basal expression in cell culture depends on the spacing bet ween the three TRE elements, located at the HTLV-1 LTR (long terminal repea l), whereas the lever of transcription activation mediated by Tax is affect ed by the number of TREs. In the presence of only one TRE, the enhancement of expression by Tax is affected by the distance between the single TRE and the transcription start site. Following CREB binding to the LTR, additiona l DNase I hypersensitive sites are generated in the region between the two distal TREs (I and II), while in the presence of Tax, such sites are genera ted also in the region between TREs II and III. Neither cooperative binding of CREB to the TREs nor preferential binding of CREB to a particular TRE w as observed. Tax binding to the CREB/TRE complex does not change the DNase I protection pattern. Taken together, these results suggest that the basal CREB-mediated transcription is determined by the number and the position of the viral TREs relative to each other. Tax protein stabilizes the protein/ DNA complex and suppresses the spacing limitations, probably by bridging be tween the CREB/TRE complexes and the basal initiation transcription complex . (C) 1999 Academic Press.