Published online 22 April 2005
Article |
COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene transcription in human microglial cells
1INSERM unité 575 Pathophysiology of Nervous System, Centre de Neurochimie 5 rue Blaise Pascal, 67084 Strasbourg, France 2Institute for Molecular Biology and Medicine, Laboratory of Molecular Virology 12 rue des Professeurs Jeener et Brachet, 6041 Gosselies, Belgium 3Unité CNRS UPR 2356 5, rue Blaise Pascal, 67084 Strasbourg, France 4Laboratory of Molecular Pharmacology, College of Pharmacy and Environmental Health Sciences Center, Oregon State University Corvallis, Oregon 97331-3507, France 5IUT Louis Pasteur de Schiltigheim, 1 Allée d'Athènes 67300 Schiltigheim, France
*To whom correspondence should be addressed. Tel: +33 388 45 66 01; Fax: +33 388 60 08 06; Email: rohr{at}neurochem.u-strasbg.fr
Received December 28, 2004. Revised April 4, 2005. Accepted April 4, 2005.
Human immunodeficiency virus type 1 (HIV-1) gene transcription is characterized by two temporally distinct phases. While the initial phase relies solely on cellular transcription factors, the subsequent phase is activated by the viral Tat transactivator. We have previously reported that the subsequent phase of viral gene transcription can be repressed by the chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2 (CTIP2) in human microglial cells [O. Rohr, D. Lecestre, S. Chasserot-Golaz, C. Marban, D. Avram, D. Aunis, M. Leid and E. Schaeffer (2003), J. Virol., 77, 5415–5427]. Here, we demonstrate that CTIP proteins also repress the initial phase of HIV-1 gene transcription, mainly supported by the cellular transcription factors Sp1 and COUP-TF in microglial cells. We report that CTIP2 represses Sp1- and COUP-TF-mediated activation of HIV-1 gene transcription and viral replication as a result of physical interactions with COUP-TF and Sp1 in microglial nuclei. Using laser confocal microscopy CTIP2 was found to colocalize with Sp1, COUP-TF and the heterochromatin-associated protein Hp1
, which is mainly detected in transcriptionally repressed heterochromatic region. Moreover, we describe that CTIP2 can be recruited to the HIV-1 promoter via its association with Sp1 bound to the GC-box sequences of the long terminal repeat (LTR). Since our findings demonstrate that CTIP2 interacts with the HIV-1 proximal promoter, it is likely that CTIP2 promotes HIV-1 gene silencing by forcing transcriptionally repressed heterochromatic environment to the viral LTR region.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Cucciolla, A. Borriello, M. Criscuolo, A. A. Sinisi, D. Bencivenga, A. Tramontano, A. C. Scudieri, A. Oliva, V. Zappia, and F. D. Ragione Histone deacetylase inhibitors upregulate p57Kip2 level by enhancing its expression through Sp1 transcription factor Carcinogenesis, March 1, 2008; 29(3): 560 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Jiang, A. Espeseth, D. J. Hazuda, and D. M. Margolis c-Myc and Sp1 Contribute to Proviral Latency by Recruiting Histone Deacetylase 1 to the Human Immunodeficiency Virus Type 1 Promoter J. Virol., October 15, 2007; 81(20): 10914 - 10923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Imai and T. Okamoto Transcriptional Repression of Human Immunodeficiency Virus Type 1 by AP-4 J. Biol. Chem., May 5, 2006; 281(18): 12495 - 12505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Goumon, A. Muller, E. Glattard, C. Marban, C. Gasnier, J.-M. Strub, S. Chasserot-Golaz, O. Rohr, G. B. Stefano, I. D. Welters, et al. Identification of Morphine-6-glucuronide in Chromaffin Cell Secretory Granules J. Biol. Chem., March 24, 2006; 281(12): 8082 - 8089. [Abstract] [Full Text] [PDF]
|
|