title: Varying modulation of HIV-1 LTR activity by Baf complexes.
abstract: The human immunodeficiency virus type 1 (HIV-1) long terminal repeat is present on both ends of the integrated viral genome and contains regulatory elements needed for transcriptional initiation and elongation. Post-integration, a highly ordered chromatin structure consisting of at least five nucleosomes, is found at the 5' long terminal repeat, the location and modification state of which control the state of active viral replication as well as silencing of the latent HIV-1 provirus. In this context, the chromatin remodeling field rapidly emerges as having a critical role in the control of viral gene expression. In the current study, we focused on unique Baf subunits that are common to the most highly recognized of chromatin remodeling proteins, the SWI/SNF (switching-defective-sucrose non-fermenting) complexes. We find that at least two Baf proteins, Baf53 and Baf170, are highly regulated in HIV-1-infected cells. Previously, studies have shown that the depletion of Baf53 in uninfected cells leads to the expansion of chromosomal territories and the decompaction of the chromatin. Baf53, in the presence of HIV-1 infection, co-elutes off of a chromatographic column as a different-sized complex when compared to uninfected cells and appears to be predominantly phosphorylated. The innate function of Baf53-containing complexes appears to be transcriptionally suppressive, in that knocking down Baf53 increases viral gene expression from cells both transiently and chronically infected with HIV-1. Additionally, cdk9/cyclin T in the presence of Tat is able to phosphorylate Baf53 in vitro, implying that this posttranslationally modified form relieves the suppressive effect and allows for viral transcription to proceed.
authors.affiliation: Department of Molecular and Microbiology, National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Van Duyne
authors.forename: Irene
authors.initials: I
authors.lastname: Guendel
authors.forename: Aarthi
authors.initials: A
authors.lastname: Narayanan
authors.forename: Edward
authors.initials: E
authors.lastname: Gregg
authors.forename: Nazly
authors.initials: N
authors.lastname: Shafagati
authors.forename: Mudit
authors.initials: M
authors.lastname: Tyagi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Easley
authors.forename: Zachary
authors.initials: Z
authors.lastname: Klase
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.forename: Kylene
authors.initials: K
authors.lastname: Kehn-Hall
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018274:Electroporation; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D016325:HIV Long Terminal Repeat; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D009707:Nucleosomes / Q000737:chemistry; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D012367:RNA, Viral / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: C116160:ACTL6A protein, human; D000199:Actins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D034741:RNA, Small Interfering; D012367:RNA, Viral; C101682:SMARCC2 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D054303:HIV Reverse Transcriptase