The HTLV-1 Tax protein: revealing mechanisms of transcriptional activation through histone acetylation and nucleosome disassembly.
The human T-cell leukemia virus, type-1 (HTLV-1)-encoded Tax protein is required for high-level transcription of the virus. Tax function is strictly dependent upon the phosphorylated form of the cellular transcription factor CREB (pCREB), and together they bind novel cAMP response elements located within the viral promoter. The DNA-bound Tax/pCREB complex recruits the cellular coactivators CBP/p300, which are essential for viral gene expression. The coactivators, via their histone acetyltransferase activity, function to promote changes in chromatin architecture that are permissive to transcriptional activation. Tax expression in vivo recruits p300 to the HTLV-1 promoter and correlates with depletion of nucleosomes from the integrated provirus. We recently developed a novel in vitro, chromatin-based experimental system that recapitulates the eviction of nucleosomes from the HTLV-1 promoter observed in vivo. These assays establish the essential function of Tax/pCREB recruitment of CBP/p300, and concomitant histone acetylation, in the nucleosome disassembly process. These observations are of particular significance, as Tax mediates disassembly of the full nucleosome octamer independent of transcriptional activity and ATP utilization. Instead, nucleosome eviction is absolutely dependent upon acetyl CoA and the histone chaperone Nap1. In this review, we will discuss HTLV-1, Tax transactivation, and our recent findings that uncover the critical role of Tax in promoting chromatin transitions that accompany activation of viral transcription. We will describe the phenomenon of acetylation-dependent promoter nucleosome disassembly and the emerging view that the formation of nucleosome-free promoter regions may represent a general prerequisite for transcriptional activation in eukaryotes.
Department of Biochemistry and Molecular Biology, Campus Box 1870, Colorado State University, Fort Collins, CO 80523-1870, USA. Jennifer.Nyborg@ColoState.Edu
Jennifer K
JK
Nyborg
Dinaida
D
Egan
Neelam
N
Sharma
D000107:Acetylation; D000818:Animals; D016356:Gene Products, tax / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism*; D015533:Transcriptional Activation
D016356:Gene Products, tax; D006657:Histones; D009707:Nucleosomes