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(Received for publication, August 4, 1997, and in revised form, September 22, 1997)
From Unité 338 INSERM, 5 rue Blaise Pascal,
67084 Strasbourg Cedex, France
We have recently reported that chicken ovalbumin
upstream promoter transcription factor (COUP-TF) activates human
immunodeficiency virus type 1 (HIV-1) gene transcription in glial and
neuronal cells. Here, we have examined the role of COUP-TF in
microglial cells, the major target cells for HIV-1 infection in brain.
We show that COUP-TF activates gene expression from both the
lymphotropic LAI and the macrophage-tropic JR-FL HIV-1 strains.
Although COUP-TF binds to the
Volume 272, Number 49,
Issue of December 5, 1997
pp. 31149-31155
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
COUP-TF and Sp1 Interact and Cooperate in the Transcriptional
Activation of the Human Immunodeficiency Virus Type 1 Long Terminal
Repeat in Human Microglial Cells
352/320 nuclear receptor responsive
element of the long terminal repeat, it functions as a transcriptional
activator by acting on the 68/+29 minimal promoter. This region is a
direct target of transcription factors Sp1 and Sp3. We report the
discovery and features of a physical and functional interplay between
COUP-TF and Sp1. Our cotransfection experiments provide evidence for a functional synergism between Sp1 and COUP-TF leading to enhanced transcriptional activity of the HIV-1 long terminal repeat through the
Sp1 element. In contrast, Sp3 functions as a repressor of Sp1- or
COUP-TF-induced activation. We further demonstrate that COUP-TF and Sp1
are capable of physically interacting, via the DNA-binding domain of
COUP-TF, in vitro and in the cell. These findings reveal
how the novel interplay of Sp1 and COUP-TF families of transcription
factors regulate HIV-1 gene expression.
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