Tax recruitment of CBP/p300, via the KIX domain, reveals a potent requirement for acetyltransferase activity that is chromatin dependent and histone tail independent.
Robust transcription of human T-cell leukemia virus type 1 (HTLV-1) genome requires the viral transactivator Tax. Although Tax has been previously shown to interact with the KIX domain of CBP/p300 in vitro, the precise functional relevance of this interaction remains unclear. Using two distinct approaches to interrupt the physical interaction between Tax and KIX, we find that Tax transactivation from chromatin templates is strongly dependent on CBP/p300 recruitment via the KIX domain. Additionally, we find that the primary functional contribution of CBP/p300 to Tax transactivation resides in the intrinsic acetyltransferase activity of the coactivators. These studies unexpectedly uncover a specific requirement for CBP/p300 acetyltransferase activity on chromatin templates assembled with nucleosomes lacking their amino-terminal tails. Together, these data indicate that the KIX domain of CBP/p300 is essential for targeting the acetyltransferase activity of the coactivator to the Tax-CREB (Tax/CREB) complex. Significantly, these observations reveal the presence of one or more CBP/p300 acetyltransferase targets that function specifically on chromatin templates, are independent of the histone tails, and are critical to Tax transactivation.
Georges
Sara A
SA
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.
Giebler
Holli A
HA
Cole
Philip A
PA
Luger
Karolin
K
Laybourn
Paul J
PJ
Nyborg
Jennifer K
JK
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001710:Biotin / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004330:Drosophila; D004926:Escherichia coli / Q000378:metabolism; D016356:Gene Products, tax / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019809:Streptavidin / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014982:Xenopus laevis / Q000378:metabolism
D002843:Chromatin; D016356:Gene Products, tax; D006657:Histones; D009687:Nuclear Proteins; D010455:Peptides; D015534:Trans-Activators; D001710:Biotin; D004247:DNA; D019809:Streptavidin; D000123:Acetyltransferases; D005982:Glutathione Transferase