This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coull, J. J. Articles by Margolis, D. M. Search for Related Content PubMed PubMed Citation Articles by Coull, J. J. Articles by Margolis, D. M.

Journal of Virology, August 2000, p. 6790-6799, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Human Factors YY1 and LSF Repress the Human Immunodeficiency Virus Type 1 Long Terminal Repeat via Recruitment of Histone Deacetylase 1

Jason J. Coull,¹ Fabio Romerio,² Jian-Min Sun,³ Janet L. Volker,⁴ Katherine M. Galvin,^5, James R. Davie,³ Yang Shi,⁵ Ulla Hansen,^4, and David M. Margolis^1,*

Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113¹; Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201²; Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3E OW3³; and Division of Molecular Genetics, Dana-Farber Cancer Institute and Harvard Medical School,⁴ and Department of Pathology, Harvard Medical School,⁵ Boston, Massachusetts 02115

Received 4 November 1999/Accepted 27 April 2000

Enigmatic mechanisms restore the resting state in activated lymphocytes following human immunodeficiency virus type 1 (HIV-1) infection, rarely allowing persistent nonproductive infection. We detail a mechanism whereby cellular factors could establish virological latency. The transcription factors YY1 and LSF cooperate in repression of transcription from the HIV-1 long terminal repeat (LTR). LSF recruits YY1 to the LTR via the zinc fingers of YY1. The first two zinc fingers were observed to be sufficient for this interaction in vitro. A mutant of LSF incapable of binding DNA blocked repression. Like other transcriptional repressors, YY1 can function via recruitment of histone deacetylase (HDAC). We find that HDAC1 copurifies with the LTR-binding YY1-LSF repressor complex, the domain of YY1 that interacts with HDAC1 is required to repress the HIV-1 promoter, expression of HDAC1 augments repression of the LTR by YY1, and the deacetylase inhibitor trichostatin A blocks repression mediated by YY1. This novel link between HDAC recruitment and inhibition of HIV-1 expression by YY1 and LSF, in the natural context of a viral promoter integrated into chromosomal DNA, is the first demonstration of a molecular mechanism of repression of HIV-1. YY1 and LSF may establish transcriptional and virological latency of HIV, a state that has recently been recognized in vivo and has significant implications for the long-term treatment of AIDS.

---

^* Corresponding author. University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9113. Phone: (214) 648-3593. Fax: (214) 648-0231. E-mail: david.margolis{at}emailswmed.edu.

Present address: Millennium Pharmaceuticals Inc., Cambridge, MA 02139.

Present address: Department of Biology, Boston University, Boston, MA 02215.

---

Journal of Virology, August 2000, p. 6790-6799, Vol. 74, No. 15
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

• Poleshko, A., Palagin, I., Zhang, R., Boimel, P., Castagna, C., Adams, P. D., Skalka, A. M., Katz, R. A. (2008). Identification of Cellular Proteins That Maintain Retroviral Epigenetic Silencing: Evidence for an Antiviral Response. J. Virol. 82: 2313-2323 [Abstract] [Full Text]  
• Katz, R. A., Jack-Scott, E., Narezkina, A., Palagin, I., Boimel, P., Kulkosky, J., Nicolas, E., Greger, J. G., Skalka, A. M. (2007). High-Frequency Epigenetic Repression and Silencing of Retroviruses Can Be Antagonized by Histone Deacetylase Inhibitors and Transcriptional Activators, but Uniform Reactivation in Cell Clones Is Restricted by Additional Mechanisms. J. Virol. 81: 2592-2604 [Abstract] [Full Text]  
• Mokrani, H., Sharaf el dein, O., Mansuroglu, Z., Bonnefoy, E. (2006). Binding of YY1 to the Proximal Region of the Murine Beta Interferon Promoter Is Essential To Allow CBP Recruitment and K8H4/K14H3 Acetylation on the Promoter Region after Virus Infection. Mol. Cell. Biol. 26: 8551-8561 [Abstract] [Full Text]  
• Luke, M. P.-s., Sui, G., Liu, H., Shi, Y. (2006). Yin Yang 1 Physically Interacts with Hoxa11 and Represses Hoxa11-dependent Transcription. J. Biol. Chem. 281: 33226-33232 [Abstract] [Full Text]  
• Mahmoudi, T., Parra, M., Vries, R. G. J., Kauder, S. E., Verrijzer, C. P., Ott, M., Verdin, E. (2006). The SWI/SNF Chromatin-remodeling Complex Is a Cofactor for Tat Transactivation of the HIV Promoter. J. Biol. Chem. 281: 19960-19968 [Abstract] [Full Text]  
• Imai, K., Okamoto, T. (2006). Transcriptional Repression of Human Immunodeficiency Virus Type 1 by AP-4. J. Biol. Chem. 281: 12495-12505 [Abstract] [Full Text]  
• Kang, H. C., Chae, J. H., Lee, Y. H., Park, M.-A., Shin, J. H., Kim, S.-H., Ye, S.-K., Cho, Y. S., Fiering, S., Kim, C. G. (2005). Erythroid Cell-Specific {alpha}-Globin Gene Regulation by the CP2 Transcription Factor Family. Mol. Cell. Biol. 25: 6005-6020 [Abstract] [Full Text]  
• Ylisastigui, L., Kaur, R., Johnson, H., Volker, J., He, G., Hansen, U., Margolis, D. (2005). Mitogen-Activated Protein Kinases Regulate LSF Occupancy at the Human Immunodeficiency Virus Type 1 Promoter. J. Virol. 79: 5952-5962 [Abstract] [Full Text]  
• Calomme, C., Dekoninck, A., Nizet, S., Adam, E., Nguyen, T. L.-A., Van Den Broeke, A., Willems, L., Kettmann, R., Burny, A., Van Lint, C. (2004). Overlapping CRE and E Box Motifs in the Enhancer Sequences of the Bovine Leukemia Virus 5' Long Terminal Repeat Are Critical for Basal and Acetylation-Dependent Transcriptional Activity of the Viral Promoter: Implications for Viral Latency. J. Virol. 78: 13848-13864 [Abstract] [Full Text]  
• de Rozieres, S., Mathiason, C. K., Rolston, M. R., Chatterji, U., Hoover, E. A., Elder, J. H. (2004). Characterization of a Highly Pathogenic Molecular Clone of Feline Immunodeficiency Virus Clade C. J. Virol. 78: 8971-8982 [Abstract] [Full Text]  
• Lassen, K. G., Bailey, J. R., Siliciano, R. F. (2004). Analysis of Human Immunodeficiency Virus Type 1 Transcriptional Elongation in Resting CD4+ T Cells In Vivo. J. Virol. 78: 9105-9114 [Abstract] [Full Text]  
• Krishnan, V., Zeichner, S. L. (2004). Host Cell Gene Expression during Human Immunodeficiency Virus Type 1 Latency and Reactivation and Effects of Targeting Genes That Are Differentially Expressed in Viral Latency. J. Virol. 78: 9458-9473 [Abstract] [Full Text]  
• Shestakova, E. A., Mansuroglu, Z., Mokrani, H., Ghinea, N., Bonnefoy, E. (2004). Transcription factor YY1 associates with pericentromeric {gamma}-satellite DNA in cycling but not in quiescent (G0) cells. Nucleic Acids Res 32: 4390-4399 [Abstract] [Full Text]  
• Cicatiello, L., Addeo, R., Sasso, A., Altucci, L., Petrizzi, V. B., Borgo, R., Cancemi, M., Caporali, S., Caristi, S., Scafoglio, C., Teti, D., Bresciani, F., Perillo, B., Weisz, A. (2004). Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G1 by Inducing Transcriptional Derepression via c-Jun/c-Fos/Estrogen Receptor (Progesterone Receptor) Complex Assembly to a Distal Regulatory Element and Recruitment of Cyclin D1 to Its Own Gene Promoter. Mol. Cell. Biol. 24: 7260-7274 [Abstract] [Full Text]  
• Rohr, O., Marban, C., Aunis, D., Schaeffer, E. (2003). Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells. J. Leukoc. Biol. 74: 736-749 [Abstract] [Full Text]  
• Brooks, D. G., Arlen, P. A., Gao, L., Kitchen, C. M. R., Zack, J. A. (2003). Identification of T cell-signaling pathways that stimulate latent HIV in primary cells. Proc. Natl. Acad. Sci. USA 100: 12955-12960 [Abstract] [Full Text]  
• Weill, L., Shestakova, E., Bonnefoy, E. (2003). Transcription Factor YY1 Binds to the Murine Beta Interferon Promoter and Regulates Its Transcriptional Capacity with a Dual Activator/Repressor Role. J. Virol. 77: 2903-2914 [Abstract] [Full Text]  
• Coull, J. J., He, G., Melander, C., Rucker, V. C., Dervan, P. B., Margolis, D. M. (2002). Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides. J. Virol. 76: 12349-12354 [Abstract] [Full Text]  
• Quivy, V., Adam, E., Collette, Y., Demonte, D., Chariot, A., Vanhulle, C., Berkhout, B., Castellano, R., de Launoit, Y., Burny, A., Piette, J., Bours, V., Van Lint, C. (2002). Synergistic Activation of Human Immunodeficiency Virus Type 1 Promoter Activity by NF-{kappa}B and Inhibitors of Deacetylases: Potential Perspectives for the Development of Therapeutic Strategies. J. Virol. 76: 11091-11103 [Abstract] [Full Text]  
• He, G., Margolis, D. M. (2002). Counterregulation of Chromatin Deacetylation and Histone Deacetylase Occupancy at the Integrated Promoter of Human Immunodeficiency Virus Type 1 (HIV-1) by the HIV-1 Repressor YY1 and HIV-1 Activator Tat. Mol. Cell. Biol. 22: 2965-2973 [Abstract] [Full Text]  
• Peng, Y., Jahroudi, N. (2002). The NFY transcription factor functions as a repressor and activator of the von Willebrand factor promoter. Blood 99: 2408-2417 [Abstract] [Full Text]  
• Drouin, E. E., Schrader, C. E., Stavnezer, J., Hansen, U. (2002). The Ubiquitously Expressed DNA-Binding Protein Late SV40 Factor Binds Ig Switch Regions and Represses Class Switching to IgA. J. Immunol. 168: 2847-2856 [Abstract] [Full Text]  
• Guo, J., Casolaro, V., Seto, E., Yang, W.-M., Chang, C., Seminario, M.-C., Keen, J., Georas, S. N. (2001). Yin-Yang 1 Activates Interleukin-4 Gene Expression in T Cells. J. Biol. Chem. 276: 48871-48878 [Abstract] [Full Text]  
• Santiago, F. S., Lowe, H. C., Bobryshev, Y. V., Khachigian, L. M. (2001). Induction of the Transcriptional Repressor Yin Yang-1 by Vascular Cell Injury. AUTOCRINE/PARACRINE ROLE OF ENDOGENOUS FIBROBLAST GROWTH FACTOR-2. J. Biol. Chem. 276: 41143-41149 [Abstract] [Full Text]