Characterization of a glial cell-specific DNA-protein complex formed with the human T cell lymphotropic virus type I (HTLV-I) enhancer

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

“…Although the three repeats are similar to one another with respect to nucleotide sequence, mutagenesis of the HTLV-I LTR has demonstrated that the 21 bp repeats are not functionally equivalent (Tillmann et al, 1994, Wessner et al, 1995, 1997Barnhart et al, 1997;Yao and Wigdahl, 2000;Yao and Wigdahl, unpublished observations). Several cellular proteins of the ATF/CREB family, members of the AP-1 transcriptional complex, and the transcription factors Sp1 and Sp3 have been demonstrated to interact with TRE-1 (Fujii et al, 1995;Wessner et al, 1995 (Fig. 4).…”

“…In contrast, the regulatory region located in the R/U5 region downstream of the transcriptional initiation site is not responsive to Tax. transfection analyses have demonstrated that the Tax responsiveness of the 21 bp repeats requires domains A and B or B and C. Domain B, the most pivotal of the three with respect to Tax responsiveness, is comprised of the ®rst ®ve base pairs of the cyclic AMP response element (CRE), TGACGTCA (Seeler et al, 1993). Although the three repeats are similar to one another with respect to nucleotide sequence, mutagenesis of the HTLV-I LTR has demonstrated that the 21 bp repeats are not functionally equivalent (Tillmann et al, 1994, Wessner et al, 1995, 1997Barnhart et al, 1997;Yao and Wigdahl, 2000;Yao and Wigdahl, unpublished observations). Several cellular proteins of the ATF/CREB family, members of the AP-1 transcriptional complex, and the transcription factors Sp1 and Sp3 have been demonstrated to interact with TRE-1 (Fujii et al, 1995;Wessner et al, 1995 (Fig.…”

“…3). ATF/CREB transcription factors have been shown to bind to each of the 21 bp repeats, while activator protein-1 (AP-1) has been shown to bind speci®cally to the pc repeat, and Sp1/Sp3 factors have been shown to bind speci®cally to the pp repeat (Wessner et al, 1995 (Fig. 4).…”

“…HTLV-I LTR-driven gene expression within target cell populations is dependent on cis-acting enhancer sequences comprised of three 21 bp imperfectly repeated elements collectively designated as Tax-responsive element 1 (TRE-1) located within the U3 region of the LTR at positions À251 to À231 (promoter distal (pd), repeat I), À203 to À183 (promoter central (pc), repeat II), and À103 to À83 (promoter proximal (pp), repeat III) relative to the transcriptional start site (Brady et al, 1987;Tillmann et al, 1994;Wessner et al, 1995Barnhart et al, 1997;reviewed in Yao and Wigdahl, 2000) (Fig. 3).…”

Human T cell lymphotropic virus type I genomic expression and impact on intracellular signaling pathways during neurodegenerative disease and leukemia

“…Electrophoretic mobility shift (EMS) analyses performed utilizing oligonucleotides corresponding to each of the three individual repeat elements and nuclear extracts from several HTLV-I target cell lines have resulted in the detection of two DNA-protein complexes formed primarily with the promoter proximal repeat, and other complexes common to each 21-bp repeat (69)(70)(71)(72)(73). Antibody supershift and consensus oligonucleotide competition EMS analyses have shown that the DNA-protein complexes common to each 21-bp repeat consist of ATF/CREB family members (CREB, CREM, ATF-1, and ATF-2), whereas DNAprotein complexes unique to the promoter proximal repeat involved Sp1 and Sp3 (69,(72)(73)(74) (76). EMS analyses (Yao and Wigdahl, unpublished results) indicated that while mutation in the conserved C domain of the promoter proximal repeat substantially reduced the binding of Sp factors, mutation of the AGGCGT sequence only marginally affected Sp binding to the proximal repeat.…”