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 ability to interact with DNA in a structure-specific manner and with DNA, binding transcriptional activators via distinct protein-protein interaction surfaces. To investigate the hypothesis that HMG I/Y may have a role in human immunodeficiency virus type 1 (HIV-1) expression, we have analyzed whether HMG I/Y interacts with the 5' long terminal repeat and whether this interaction can modulate transcription factor binding. Using purified recombinant HMG I, we have identified several high-affinity binding sites which overlap important transcription factor binding sites. One of these HMG I binding sites coincides with an important binding site for AP-1 located downstream of the transcriptional start site, in the 5' untranslated region at the boundary of a positioned nucleosome. HMG I binding to this composite site inhibits 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-1 transcription factor to this AP-1 binding site. We also report the novel finding that a component present in this inducible AP-1 complex is ATF-3. Taken together, these results argue that HMG I may play a fundamental role in HIV-1 expression by determining the nature of transcription factor-promoter interactions.
Henderson
A
A
The John Curtin School of Medical Research, the Australian National University, Canberra, Australian Capital Territory 2601, Australia.
Bunce
M
M
Siddon
N
N
Reeves
R
R
Tremethick
D J
DJ
D020121:5' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D051700:Activating Transcription Factor 3; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D025741:HMGA1a Protein; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011533:Proviruses / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020121:5' Untranslated Regions; D051700:Activating Transcription Factor 3; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D025741:HMGA1a Protein; D013755:Tetradecanoylphorbol Acetate