A NUCLEAR MATRIX-SPECIFIC FACTOR THAT BINDS A SPECIFIC SEGMENT OF THENEGATIVE REGULATORY ELEMENT (NRE) OF HIV-1 LTR AND INHIBITS NF-KAPPA-B ACTIVITY

The negative regulatory element (NRE) of human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR) is a defined region that has been reported to downregulate LTR-directed HIV gene expression, Howev er, information on the precise role of this region in regulating HIV g ene transcription is lacking. We have investigated the possibility tha t these NRE sequences regulate HIV transcription by a mechanism mediat ed through a nuclear matrix-specific DNA-protein interaction. We find a nuclear matrix attachment region (MAR) present within the NRE of the HIV-1 LTR that recognizes a sequence-specific DNA-binding protein pre sent in the nuclear matrix of HIV infected cells. Moreover, we also sh ow that the purified DNA-binding nuclear matrix protein (NMP) specific ally represses the DNA-binding activity of NF-kappa B. It is likely th at the MAR and MAR-enriched specific DNA-binding NMP are brought into juxtaposition by the non-chromatin scaffolding of the nucleus, thus in fluencing NF-kappa B (and other nuclear proteins) DNA-binding activity through protein-protein and protein-DNA interactions. Our data sugges t that one possible role of the NRE could be to act as a matrix attach ment site in the nuclear matrix, thus, allowing interaction with a seq uence-specific trans-acting factor. The negative effect on NF-kappa B activity due to this MAR-NMP-specific interaction provides a mechanism by which the NRE downregulates HIV gene expression.