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Closed chromatin architecture is induced by an RNA duplex targeting the HIV-1 promoter region

Suzkuki, Kazuo; Juelich, Torsten; Lim, Heidi; Ishida, Takaomi; Watanebe, Toshiki; Cooper, David A; Rao, Sudha; Kelleher, Anthony D

Description

In some mammalian systems small interfering RNAs (siRNA) targeting homologous sequences in promoter regions of genes induce transcriptional gene silencing (TGS). We have previously reported the induction of TGS by an siRNA (prom-A siRNA) targeting the tandem NF-κB-binding motifs within the human immunodeficiency virus, type 1 (HIV-1), promoter region. Here we report that induction of TGS by prom-A siRNA is accompanied by immediate and sustained local recruitment of Argonaute-1 (Ago1), histone...[Show more]

dc.contributor.authorSuzkuki, Kazuo
dc.contributor.authorJuelich, Torsten
dc.contributor.authorLim, Heidi
dc.contributor.authorIshida, Takaomi
dc.contributor.authorWatanebe, Toshiki
dc.contributor.authorCooper, David A
dc.contributor.authorRao, Sudha
dc.contributor.authorKelleher, Anthony D
dc.date.accessioned2015-12-08T22:10:28Z
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/1885/29349
dc.description.abstractIn some mammalian systems small interfering RNAs (siRNA) targeting homologous sequences in promoter regions of genes induce transcriptional gene silencing (TGS). We have previously reported the induction of TGS by an siRNA (prom-A siRNA) targeting the tandem NF-κB-binding motifs within the human immunodeficiency virus, type 1 (HIV-1), promoter region. Here we report that induction of TGS by prom-A siRNA is accompanied by immediate and sustained local recruitment of Argonaute-1 (Ago1), histone deacetylase-1 (HDAC1), and induction of dimethylation of histone 3 at lysine 9 (H3K9me2), processes known to be associated with transcriptional silencing. Elevated levels of H3K9me2 and HDAC1 spread upstream of the target sequence, and elevated H3K9me2 levels also spread downstream into the coding region. Moreover, this siRNA induces an immediate change in DNA accessibility to restriction enzyme digestion in the region of the transcription initiation site of the HIV-1. This change in accessibility is because of the relocation of a nucleosome known to be associated with this region of the integrated pro-virus. Although there is a theoretical possibility that the observed viral suppression could be mediated by the PTGS mechanism with this siRNA acting at the 3′-long term repeat of the virus, we demonstrate that this siRNA, and three other U3 targeted siRNAs, are inefficient inducers of PTGS. These data strongly suggest that siRNA targeting the promoter region acts predominantly at a site within the 5′-long term repeat of HIV to induce transcriptional silencing and alterations to chromatin structure of the HIV promoter region that extend well beyond the immediate siRNA target site. These induced changes are consistent with those described in latent HIV-1 infection.
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc
dc.sourceJournal of Biological Chemistry
dc.subjectKeywords: Amino acids; Chromosomes; Genes; Genetic engineering; Mammals; Nucleic acids; Organic acids; Programming theory; RNA; Turbomachine blades; Viruses; Binding motifs; Chromatin structures; Coding regions; Elevated levels; Histone deacetylase; Homologous sequ
dc.titleClosed chromatin architecture is induced by an RNA duplex targeting the HIV-1 promoter region
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume283
dc.date.issued2008
local.identifier.absfor110799 - Immunology not elsewhere classified
local.identifier.ariespublicationu6800332xPUB64
local.type.statusPublished Version
local.contributor.affiliationSuzkuki, Kazuo, St Vincent's Hospital
local.contributor.affiliationJuelich, Torsten, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLim, Heidi, St Vincent's Hospital
local.contributor.affiliationIshida, Takaomi, University of Tokyo
local.contributor.affiliationWatanebe, Toshiki, University of Tokyo
local.contributor.affiliationCooper, David A, University of New South Wales
local.contributor.affiliationRao, Sudha, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKelleher, Anthony D, University of New South Wales
local.description.embargo2037-12-31
local.bibliographicCitation.issue34
local.bibliographicCitation.startpage23353
local.bibliographicCitation.lastpage23363
local.identifier.doi10.1074/jbc.M709651200
dc.date.updated2015-12-08T07:32:38Z
local.identifier.scopusID2-s2.0-53149132028
CollectionsANU Research Publications

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