Transcription Factor Binding and Histone Modifications on the Integrated Proviral Promoter in Human T-cell Leukemia Virus-I-infected T-cells

The human T-cell leukemia virus (HTLV-I)-encoded Tax protein is a potent transcriptional activator that stimulates expression of the integrated provirus. Biochemical studies indicate that Tax, together with cellular transcription factors, interacts with viral cAMP-response element enhancer elements...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2002-12, Vol.277 (51), p.49459-49465
Main Authors: Lemasson, Isabelle, Polakowski, Nicholas J., Laybourn, Paul J., Nyborg, Jennifer K.
Format: Article
Language:English
Subjects:
Acetylation
Chromatin - metabolism
Cyclic AMP - metabolism
Genes, Viral
Histones - metabolism
Human T-lymphotropic virus 1 - metabolism
Humans
Models, Genetic
Nuclear Proteins - metabolism
Plasmids - metabolism
Polymerase Chain Reaction
Precipitin Tests
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
Single-Strand Specific DNA and RNA Endonucleases - metabolism
T-Lymphocytes - virology
Trans-Activators - metabolism
Transcription Factor AP-1 - metabolism
Transcription Factors - metabolism
Transcription, Genetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The human T-cell leukemia virus (HTLV-I)-encoded Tax protein is a potent transcriptional activator that stimulates expression of the integrated provirus. Biochemical studies indicate that Tax, together with cellular transcription factors, interacts with viral cAMP-response element enhancer elements to recruit the pleiotropic coactivators CREB-binding protein and p300. Histone acetylation by these coactivators has been shown to play a major role in activating HTLV-I transcription from chromatin templates in vitro. However, the extent of histone modification and the precise identity of the cellular regulatory proteins bound at the HTLV-I promoter in vivo is not known. Chromatin immunoprecipitation analysis was used to investigate factor binding and histone modification at the integrated HTLV-I provirus in infected T-cells (SLB-1). These studies reveal the presence of Tax, a variety of ATF/CREB and AP-1 family members (CREB, CREB-2, ATF-1, ATF-2, c-Fos, and c-Jun), and both p300 and CREB-binding protein at the HTLV-I promoter. Consistent with the binding of these coactivators, we observed histone H3 and H4 acetylation at three regions within the proviral genome. Histone deacetylases were also present at the viral promoter and, following their inhibition, we observe an increase in histone H4 acetylation on the HTLV-I promoter and a concomitant increase in viral RNA. Together, these results suggest that a variety of transcriptional activators, coactivators, and histone deacetylases participate in the regulation of HTLV-I transcription in infected T-cells.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M209566200