HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 42, 43604-43613, October 15, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/42/43604    most recent M408069200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kiefer, H. L. B. Articles by Viglianti, G. A. Search for Related Content PubMed PubMed Citation Articles by Kiefer, H. L. B. Articles by Viglianti, G. A. Social Bookmarking                      What's this?

Retinoic Acid Inhibition of Chromatin Remodeling at the Human Immunodeficiency Virus Type 1 Promoter

UNCOUPLING OF HISTONE ACETYLATION AND CHROMATIN REMODELING^*

Heather L. B. Kiefer¶, Timothy M. Hanley, Jennifer E. Marcello||, A. G. Karthik, and Gregory A. Viglianti**

From the Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118

All-trans retinoic acid (RA) represses HIV-1 transcription and replication in cultured monocytic cells and in primary monocyte-derived macrophages. Here we examine the role of histone acetylation and chromatin remodeling in RA-mediated repression. RA pretreatment of latently infected U1 promonocytes inhibits HIV-1 expression in response to the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA). TSA is thought to activate HIV-1 transcription by inducing histone hyperacetylation within a regulatory nucleosome, nuc-1, positioned immediately downstream from the transcription start site. Acetylation of nuc-1 is thought to be a critical step in activation that precedes nuc-1 remodeling and, subsequently, transcriptional initiation. Here we demonstrate that TSA treatment induces H3 and H4 hyperacetylation and nuc-1 remodeling. Although RA pretreatment inhibits nuc-1 remodeling and HIV-1 transcription, it has no effect on histone acetylation. This suggests that acetylation and remodeling are not obligatorily coupled. We also show that growth of U1 cells in retinoid-deficient medium induces nuc-1 remodeling and HIV-1 expression but does not induce histone hyperacetylation. These findings suggest that remodeling, not histone hyperacetylation, is the limiting step in transcriptional activation in these cells. Together, these data suggest that RA signaling maintains the chromatin structure of the HIV-1 promoter in a transcriptionally non-permissive state that may contribute to the establishment of latency in monocyte/macrophages.

Received for publication, July 16, 2004 , and in revised form, August 4, 2004.

^* This work was supported by Grant HL57882 from the NHLBI, National Institutes of Health and Grant AI49098 from the NIAID, National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

^¶ Current address: Intelligent Medical Devices, LLC, Cambridge, MA 02141.

^|| Current address: Dept. of Biostatistics, University of North Carolina, Chapel Hill, NC 27599.

^** To whom correspondence should be addressed. Tel.: 617-638-7790; Fax: 617-638-4286; E-mail: gviglian{at}bu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Rodeheffer, V. von Messling, S. Milot, F. Lepine, A. R. Manges, and B. J. Ward Disease Manifestations of Canine Distemper Virus Infection in Ferrets Are Modulated by Vitamin A Status J. Nutr., August 1, 2007; 137(8): 1916 - 1922. [Abstract] [Full Text] [PDF]