The coactivators CBP/p300 and the histone chaperone NAP1 promote transcription-independent nucleosome eviction at the HTLV-1 promoter.
The human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma. The multifunctional virally encoded oncoprotein Tax is responsible for malignant transformation and potent activation of HTLV-1 transcription. Tax, in complex with phosphorylated cAMP response element binding protein (pCREB), strongly recruits the cellular coactivators CREB binding protein (CBP)/p300 to the viral promoter concomitant with transcriptional activation. Although the mechanism of activator/coactivator-mediated transcriptional activation is poorly understood, the recruitment of CBP/p300 by regulatory factors appears to function, in part, by promoting changes in chromatin architecture that are permissive to transcriptional activation. Here, we show that CBP/p300 recruitment promotes histone acetylation and eviction of the histone octamer from the chromatin-assembled HTLV-1 promoter template in vitro. Nucleosome disassembly is strictly acetyl-CoA dependent and is not linked to ATP utilization. We find that the histone chaperone, nucleosome assembly protein 1 (NAP1), cooperates with CBP/p300 in eviction of the acetylated histones from the chromatin template. These findings reveal a unique mechanism in which the DNA-bound Tax/pCREB complex recruits CBP/p300, and together with NAP1, the coactivators cooperate to dramatically reduce nucleosome occupancy at the viral promoter in an acetylation-dependent and transcription-independent fashion.
Sharma
Neelam
N
Department of Biochemistry and Molecular Biology, Campus Box 1870, Colorado State University, Fort Collins, CO 80523, USA.
Nyborg
Jennifer K
JK
D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000107:Acetylation / Q000187:drug effects; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D056490:Nucleosome Assembly Protein 1; D009707:Nucleosomes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D016356:Gene Products, tax; D006657:Histones; D018832:Molecular Chaperones; C533557:NAP1L1 protein, human; C533554:Nap1 protein, Drosophila; D009687:Nuclear Proteins; D056490:Nucleosome Assembly Protein 1; D009707:Nucleosomes; D010750:Phosphoproteins; D000105:Acetyl Coenzyme A; D050880:p300-CBP Transcription Factors