A nuclear factor is required for transactivation of HTLV-I gene expression

Human T-cell Leukemia Virus (HTLV-I) gene expression is regulated by both constitutive and inducible enhancer elements. The viral components required for inducible enhancer function include the cis-acting 21 bp motifs present three times within the U3 region of the LTR and the trans-acting 40 kD tax protein encoded by the 3' end of the viral genome. A gel electrophoresis protein-DNA binding assay was used to identify the interaction of nuclear factors with the 21 bp element. Specific protein-DNA interactions were observed in all cell lines examined. No differences were observed in the binding patterns obtained from extracts prepared from those cell lines that did or did not express the tax protein. Dimethyl sulfate (DMS) interference analysis indicates that a nuclear factor contacts the guanine residues in the sequence GGCGTTGAGG. Oligonucleotide directed mutagenesis of the putative protein-DNA contact points markedly reduces the transactivation response. These results support an indirect mechanism for transactivation whereby regulation of HTLV-I gene expression is controlled by the interaction of the cis-acting 21 bp motif with a nuclear factor activated by tax.