title: Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat.
abstract: A unique aspect of the retrovirus life cycle is the obligatory integration of the provirus into host cell chromosomes. Unlike viruses that do not integrate, retroviruses must conserve an ability to activate transcription from a chromatin context. Human immunodeficiency virus (HIV)-1 encodes an unusual and an unusually potent transcriptional transactivator, Tat, which binds to a nascent viral leader RNA, TAR. The action of Tat has been well studied in various reductive model systems; however, the physiological mechanism through which Tat gains access to chromatin-associated proviral long terminal repeats (LTRs) is not understood. We show here that a nuclear histone acetyltransferase activity associates with Tat. Intracellularly, we found that Tat forms a ternary complex with p300 and P/CAF, two histone acetyltransferases (HATs). A murine cell defect in Tat transactivation of the HIV-1 LTR was linked to the reduced abundance of p300 and P/CAF. Thus, overexpression of p300 and P/CAF reconstituted Tat transactivation of the HIV-1 LTR in NIH3T3 cells to a level similar to that observed for human cells. By using transdominant p300 or P/CAF mutants that lack enzymatic activity, we delineated a requirement for the HAT component from the latter but not the former in Tat function. Finally, we observed that Tat-associated HAT is preferentially important for transactivation of integrated, but not unintegrated, HIV-1 LTR.
authors.affiliation: Molecular Virology Section, Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Benkirane
authors.forename: R F
authors.initials: RF
authors.lastname: Chun
authors.forename: H
authors.initials: H
authors.lastname: Xiao
authors.forename: V V
authors.initials: VV
authors.lastname: Ogryzko
authors.forename: B H
authors.initials: BH
authors.lastname: Howard
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatani
authors.forename: K T
authors.initials: KT
authors.lastname: Jeang
mesh_terms: D016475:3T3 Cells; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000502:physiology; D003001:Cloning, Molecular; D015696:Gene Products, tat / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D008018:Life Cycle Stages; D051379:Mice; D011533:Proviruses / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D014157:Transcription Factors; D016662:Virus Integration; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002843:Chromatin; D015696:Gene Products, tat; D051548:Histone Acetyltransferases; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor