The high-affinity Sp1 binding site in the HTLV-1 promoter contributes to Tax-independent basal expression.
Transcriptional activation of human T-cell leukemia virus type 1 (HTLV-1) requires many cellular proteins and the virally encoded transcription factor Tax. Tax binds the three viral cAMP-response elements (CREs) with ATF/CREB (activating transcription factor/cAMP-response element-binding protein) and recruits the cellular coactivators CBP/p300. HTLV-1 also utilizes other cellular transcription factors that bind to the promoter to regulate transcription. One of these factors, Sp1, has been shown to bind to the viral promoter at two elements; one located within the third viral CRE, and the second located between the second and third viral CREs. The functional significance of Sp1 binding at each of these regions of the viral promoter is not completely understood. We set out to characterize Sp1 binding and to evaluate the functional significance of Sp1, both in the absence and presence of Tax. We found that Sp1 binds preferentially to the element located between the second and third viral CREs, and modestly activates transcription in vitro and in vivo. Sp1 was detected at the integrated HTLV-1 promoter in vivo. Surprisingly, point mutagenesis of the strong Sp1 binding site rendered the HTLV-1 reporter plasmid insensitive to Sp1 activation, and dramatically reduced basal transcription in vivo. These data indicate a role for Sp1 in basal level transcription of HTLV-1.
Livengood
Jill A
JA
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.
Nyborg
Jennifer K
JK
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006224:Cricetinae; D016356:Gene Products, tax / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic
D016356:Gene Products, tax; D016329:Sp1 Transcription Factor