Nucleic Acids Research, Vol 24, Issue 10 1895-1900, Copyright © 1996 by Oxford University Press
T Hoover, J Mikovits, D Court, YL Liu, HF Kung and
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. However,
information on the precise role of this region in regulating HIV gone
transcription is lacking. We have investigated the possibility that these
NRE sequences regulate HIV transcription by a mechanism mediated 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 present in the nuclear
matrix of HIV infected cells. Moreover, we also show that the purified
DNA-binding nuclear matrix protein (NMP) specifically represses the
DNA-binding activity of NF-kappaB. It is likely that the MAR and
MAR-enriched specific DNA-binding NMP are brought into juxtaposition by the
non-chromatin scaffolding of the nucleus, thus influencing NF-kappaB (and
other nuclear proteins) DNA- binding activity through protein-protein and
protein-DNA interactions. Our date suggest that one possible role of the
NRE could be to act as a matrix attachment site in the nuclear matrix,
thus, allowing interaction with a sequence-specific trans-acting factor.
The negative effect on NF-kappaB activity due to this MAR-NMP-specific
interaction provides a mechanism by which the NRE downregulates HIV gene
expression.
ARTICLES
A nuclear matrix-specific factor that binds a specific segment of the negative regulatory element (NRE) of HIV-1 LTR and inhibits NF-kappa(B) activity
Intramural Research Support Program, SAIC/Frederick, Frederick, MD 21702-1201, USA.
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