AN INTERACTION BETWEEN THE DNA-BINDING DOMAINS OF RELA(P65) AND SP1 MEDIATES HUMAN-IMMUNODEFICIENCY-VIRUS GENE ACTIVATION

Induction of human immunodeficiency virus type 1 (HIV-1) gene expressi on in stimulated T cells has been attributed to the activation of the transcription factor NF-kappa B. The twice-repeated kappa B sites with in the HIV-1 long terminal repeat are in close proximity to three bind ing sites for Sp1. We have previously shown that a cooperative interac tion of NF-kappa B with Sp1 is required for the efficient stimulation of HIV-1 transcription. In this report, we define the domains of each protein responsible for this effect. Although the transactivation doma ins seemed likely to mediate this interaction, we find, surprisingly, that this interaction occurs through the putative DNA-binding domains of both proteins. Sp1 specifically interacted with the amino-terminal region of RelA(p65). Similarly, RelA bound directly to the zinc finger region of Sp1. This interaction was specific and resulted in cooperat ive DNA binding to the kappa B and Sp1 sites in the HIV-1 long termina l repeat. Furthermore, the amino-terminal region of RelA did not assoc iate with several other transcription factors, including MyoD, E12, or Kox15, another zinc finger protein. These findings suggest that the j uxtaposition of DNA-binding sites promotes a specific protein interact ion between the DNA-binding regions of these transcription factors. Th is interaction is required for HIV transcriptional activation and may provide a mechanism to allow for selective activation of kappa B-regul ated genes.