High-mobility-group protein I can modulate binding of transcription factors to the U5 region of the human immunodeficiency virus type 1 proviral promoter

HMG I/Y appears to be a multifunctional protein that relies on in its abili ty to interact with DNA in a structure-specific manner and with DNA, bindin g transcriptional activators via distinct protein-protein interaction surfa ces. To investigate the hypothesis that HMG I/Y may have a role in human im munodeficiency virus type 1 (HIV-1) expression, me have analyzed whether HM G I/Y interacts with the 5' long terminal repeat and whether this interacti on can modulate transcription factor binding, Using purified recombinant HM G I, we have identified several high-affinity binding sites which overlap i mportant transcription factor binding sites. One of these HMG I binding sit es coincides with an important binding site for AP-I located downstream of the transcriptional start site, in the 5' untranslated region at the bounda ry of a positioned nucleosome. HMG I binding to this composite site inhibit s the binding of recombinant AP 1. Consistent with this observation, using; nuclear extracts prepared from Jurkat T cells, we show that HMG I (but not HMG Y) is strongly induced upon phorbol myristate acetate stimulation and this induced HMG I appears to both selectively inhibit the binding of basal DNA-binding proteins and enhance the binding of an inducible AP-I transcri ption factor to this AP-I binding site. We also report the novel finding th at a component present in this inducible AP-1 complex is ATF-3. Taken toget her, these results argue that HMG I may play a fundamental role in HIV 1 ex pression by determining the nature of transcription factor-promoter interac tions.