RNA-Interference Components Are Dispensable for Transcriptional Silencing of the Drosophila Bithorax-Complex

Handle URI:
http://hdl.handle.net/10754/325319
Title:
RNA-Interference Components Are Dispensable for Transcriptional Silencing of the Drosophila Bithorax-Complex
Authors:
Cernilogar, Filippo M.; Burroughs, A. Maxwell; Lanzuolo, Chiara; Breiling, Achim; Imhof, Axel; Orlando, Valerio ( 0000-0002-4906-8511 )
Abstract:
Background:Beyond their role in post-transcriptional gene silencing, Dicer and Argonaute, two components of the RNA interference (RNAi) machinery, were shown to be involved in epigenetic regulation of centromeric heterochromatin and transcriptional gene silencing. In particular, RNAi mechanisms appear to play a role in repeat induced silencing and some aspects of Polycomb-mediated gene silencing. However, the functional interplay of RNAi mechanisms and Polycomb group (PcG) pathways at endogenous loci remains to be elucidated.Principal Findings:Here we show that the endogenous Dicer-2/Argonaute-2 RNAi pathway is dispensable for the PcG mediated silencing of the homeotic Bithorax Complex (BX-C). Although Dicer-2 depletion triggers mild transcriptional activation at Polycomb Response Elements (PREs), this does not induce transcriptional changes at PcG-repressed genes. Moreover, Dicer-2 is not needed to maintain global levels of methylation of lysine 27 of histone H3 and does not affect PRE-mediated higher order chromatin structures within the BX-C. Finally bioinformatic analysis, comparing published data sets of PcG targets with Argonaute-2-bound small RNAs reveals no enrichment of these small RNAs at promoter regions associated with PcG proteins.Conclusions:We conclude that the Dicer-2/Argonaute-2 RNAi pathway, despite its role in pairing sensitive gene silencing of transgenes, does not have a role in PcG dependent silencing of major homeotic gene cluster loci in Drosophila. © 2013 Cernilogar et al.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; KAUST Environmental Epigenetics Research Program (KEEP)
Citation:
Cernilogar FM, Burroughs AM, Lanzuolo C, Breiling A, Imhof A, et al. (2013) RNA-Interference Components Are Dispensable for Transcriptional Silencing of the Drosophila Bithorax-Complex. PLoS ONE 8: e65740. doi:10.1371/journal.pone.0065740.
Publisher:
Public Library of Science
Journal:
PLoS ONE
Issue Date:
13-Jun-2013
DOI:
10.1371/journal.pone.0065740
PubMed ID:
23785447
PubMed Central ID:
PMC3681981
Type:
Article
ISSN:
19326203
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorCernilogar, Filippo M.en
dc.contributor.authorBurroughs, A. Maxwellen
dc.contributor.authorLanzuolo, Chiaraen
dc.contributor.authorBreiling, Achimen
dc.contributor.authorImhof, Axelen
dc.contributor.authorOrlando, Valerioen
dc.date.accessioned2014-08-27T09:46:46Zen
dc.date.available2014-08-27T09:46:46Zen
dc.date.issued2013-06-13en
dc.identifier.citationCernilogar FM, Burroughs AM, Lanzuolo C, Breiling A, Imhof A, et al. (2013) RNA-Interference Components Are Dispensable for Transcriptional Silencing of the Drosophila Bithorax-Complex. PLoS ONE 8: e65740. doi:10.1371/journal.pone.0065740.en
dc.identifier.issn19326203en
dc.identifier.pmid23785447en
dc.identifier.doi10.1371/journal.pone.0065740en
dc.identifier.urihttp://hdl.handle.net/10754/325319en
dc.description.abstractBackground:Beyond their role in post-transcriptional gene silencing, Dicer and Argonaute, two components of the RNA interference (RNAi) machinery, were shown to be involved in epigenetic regulation of centromeric heterochromatin and transcriptional gene silencing. In particular, RNAi mechanisms appear to play a role in repeat induced silencing and some aspects of Polycomb-mediated gene silencing. However, the functional interplay of RNAi mechanisms and Polycomb group (PcG) pathways at endogenous loci remains to be elucidated.Principal Findings:Here we show that the endogenous Dicer-2/Argonaute-2 RNAi pathway is dispensable for the PcG mediated silencing of the homeotic Bithorax Complex (BX-C). Although Dicer-2 depletion triggers mild transcriptional activation at Polycomb Response Elements (PREs), this does not induce transcriptional changes at PcG-repressed genes. Moreover, Dicer-2 is not needed to maintain global levels of methylation of lysine 27 of histone H3 and does not affect PRE-mediated higher order chromatin structures within the BX-C. Finally bioinformatic analysis, comparing published data sets of PcG targets with Argonaute-2-bound small RNAs reveals no enrichment of these small RNAs at promoter regions associated with PcG proteins.Conclusions:We conclude that the Dicer-2/Argonaute-2 RNAi pathway, despite its role in pairing sensitive gene silencing of transgenes, does not have a role in PcG dependent silencing of major homeotic gene cluster loci in Drosophila. © 2013 Cernilogar et al.en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rightsArchived with thanks to PLoS ONEen
dc.subjectargonaute 2 proteinen
dc.subjectbithorax complexen
dc.subjectdiceren
dc.subjectDNAen
dc.subjecthistone H3en
dc.subjectlysineen
dc.subjectpolycomb group proteinen
dc.subjectsmall interfering RNAen
dc.subjectunclassified drugen
dc.subjectanimal cellen
dc.subjectbioinformaticsen
dc.subjectchromatin structureen
dc.subjectcontrolled studyen
dc.subjectDNA responsive elementen
dc.subjectDrosophilaen
dc.subjectgene clusteren
dc.subjectgene locusen
dc.subjectgene repressionen
dc.subjectgene silencingen
dc.subjecthistone methylationen
dc.subjectpromoter regionen
dc.subjectprotein depletionen
dc.subjectRNA interferenceen
dc.subjecttranscription initiationen
dc.subjecttransgeneen
dc.subjectArgonaute Proteinsen
dc.subjectDrosophilaen
dc.subjectDrosophila Proteinsen
dc.subjectGene Silencingen
dc.subjectHistonesen
dc.subjectMethylationen
dc.subjectPolycomb-Group Proteinsen
dc.subjectResponse Elementsen
dc.subjectRibonuclease IIIen
dc.subjectRNA Helicasesen
dc.subjectRNA Interferenceen
dc.subjectRNA, Double-Strandeden
dc.subjectTranscription, Geneticen
dc.titleRNA-Interference Components Are Dispensable for Transcriptional Silencing of the Drosophila Bithorax-Complexen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentKAUST Environmental Epigenetics Research Program (KEEP)en
dc.identifier.journalPLoS ONEen
dc.identifier.pmcidPMC3681981en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionEpigenetics and Genome Reprogramming Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italyen
dc.contributor.institutionAdolf-Butenandt Institute, Ludwig Maximilian University of Munich, Munich, Germanyen
dc.contributor.institutionDivision of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germanyen
dc.contributor.institutionCNR Institute of Neurobiology and Molecular Medicine, IRCCS Santa Lucia Foundation, Rome, Italyen
dc.contributor.institutionRIKEN Omics Science Center, RIKEN Yokohama Institute, Tsurumi-ku, Yokohama, Kanagawa, Japanen
dc.contributor.institutionMunich Center of Integrated Protein Science, Ludwig Maximilian University of Munich, Munich, Germanyen
dc.contributor.institutionNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorOrlando, Valerioen

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