Tax-dependent Displacement of Nucleosomes during Transcriptional Activation of Human T-Cell Leukemia Virus Type 1
| Autor: | Paul J. Laybourn, Isabelle Lemasson, Nicholas Polakowski, Jennifer K. Nyborg |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Gene Expression Regulation
Viral Transcriptional Activation Chromosomal Proteins Non-Histone viruses RNA polymerase II CHO Cells Biochemistry Histones Histone H3 Histone H1 Cricetinae Animals Humans Histone code Nucleosome Promoter Regions Genetic Molecular Biology Human T-lymphotropic virus 1 biology Gene Products tax Cell Biology Molecular biology Chromatin SWI/SNF Nucleosomes Histone Mutation biology.protein RNA Polymerase II Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 281:13075-13082 |
| ISSN: | 0021-9258 |
| Popis: | The human T-cell leukemia virus type 1 (HTLV-1) is integrated into the host cell DNA and assembled into nucleosomes. Within the repressive chromatin environment, the virally encoded Tax protein mediates the recruitment of the coactivators CREB-binding protein/p300 to the HTLV-1 promoter, located within the long terminal repeats (LTRs) of the provirus. These proteins carry acetyltransferase activity that is essential for strong transcriptional activation of the virus in the context of chromatin. Consistent with this, the amino-terminal tails of nucleosomal histones at the viral promoter are acetylated in Tax-expressing cells. We have developed a system in which we transfect Tax into cells carrying integrated copies of the HTLV-1 LTR driving the luciferase gene to analyze changes in "activating" histone modifications at the LTR. Unexpectedly, Tax transactivation led to an apparent reduction of these modifications at the HTLV-1 promoter and downstream region that correlates with a similar reduction in histone H3 and linker histone H1. Micrococcal nuclease protection analysis showed that less LTR-luciferase DNA is nucleosomal in Tax-expressing cells. Furthermore, nucleosome depletion correlated with RNA polymerase II recruitment and loss of SWI/SNF. The M47 Tax mutant, deficient in HTLV-1 transcriptional activation, was also defective for nucleosome depletion. Although this mutant formed complexes with CREB and p300 at the HTLV-1 promoter in vivo, it was unable to mediate RNA polymerase II recruitment or SWI/SNF displacement. These results support a model in which nucleosomes are depleted from the LTR and transcribed region during Tax-mediated transcriptional activation and correlate RNA polymerase II recruitment with nucleosome depletion. |
| Databáze: | OpenAIRE |
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