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Article: Diverse factors are involved in maintaining X chromosome inactivation

TitleDiverse factors are involved in maintaining X chromosome inactivation
Authors
Issue Date2011
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 40, p. 16699-16704 How to Cite?
AbstractX chromosome inactivation (XCI) is the most dramatic example of epigenetic silencing in eukaryotes. Once established, the inactivated X chromosome (Xi) remains silenced throughout subsequent cell divisions. Though the initiation of XCI has been studied extensively, the protein factors involved in Xi silencing and maintenance are largely unknown. Here we report the discovery of a diverse set of 32 proteins involved in maintenance of Xi silencing through a genome-wide RNAi screen. In addition, we describe the mechanistic roles of two proteins - origin recognition complex 2 (Orc2) and heterochromatin protein 1 (HP1α) - in Xi silencing. Immunofluorescence studies indicate that Orc2 and HP1α localize on Xi in mouse cells. Depletion of Orc2 by shRNA leads to the loss of both Orc2 and HP1α localization on Xi. Furthermore, the silencing of genes on Xi is disrupted in both Orc2- and HP1α-depleted cells. Finally, we show, using ChIP assay, that the localization of HP1α and Orc2 to the promoter regions of Xi-silenced genes is interdependent. These findings reveal a diverse set of proteins involved in Xi silencing, show how Orc2 and HP1α impact Xi silencing, and provide a basis for future studies on the maintenance of Xi silencing.
Persistent Identifierhttp://hdl.handle.net/10722/184146
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, KMen_US
dc.contributor.authorZhang, Hen_US
dc.contributor.authorMalureanu, Len_US
dc.contributor.authorVan Deursen, Jen_US
dc.contributor.authorZhang, Zen_US
dc.date.accessioned2013-06-25T03:00:20Z-
dc.date.available2013-06-25T03:00:20Z-
dc.date.issued2011en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 40, p. 16699-16704en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/184146-
dc.description.abstractX chromosome inactivation (XCI) is the most dramatic example of epigenetic silencing in eukaryotes. Once established, the inactivated X chromosome (Xi) remains silenced throughout subsequent cell divisions. Though the initiation of XCI has been studied extensively, the protein factors involved in Xi silencing and maintenance are largely unknown. Here we report the discovery of a diverse set of 32 proteins involved in maintenance of Xi silencing through a genome-wide RNAi screen. In addition, we describe the mechanistic roles of two proteins - origin recognition complex 2 (Orc2) and heterochromatin protein 1 (HP1α) - in Xi silencing. Immunofluorescence studies indicate that Orc2 and HP1α localize on Xi in mouse cells. Depletion of Orc2 by shRNA leads to the loss of both Orc2 and HP1α localization on Xi. Furthermore, the silencing of genes on Xi is disrupted in both Orc2- and HP1α-depleted cells. Finally, we show, using ChIP assay, that the localization of HP1α and Orc2 to the promoter regions of Xi-silenced genes is interdependent. These findings reveal a diverse set of proteins involved in Xi silencing, show how Orc2 and HP1α impact Xi silencing, and provide a basis for future studies on the maintenance of Xi silencing.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshAnimalsen_US
dc.subject.meshChromatin Immunoprecipitationen_US
dc.subject.meshChromosomal Proteins, Non-Histone - Genetics - Metabolismen_US
dc.subject.meshDna Primers - Geneticsen_US
dc.subject.meshFluorescent Antibody Techniqueen_US
dc.subject.meshGreen Fluorescent Proteins - Genetics - Metabolismen_US
dc.subject.meshIn Situ Hybridization, Fluorescenceen_US
dc.subject.meshMiceen_US
dc.subject.meshOligonucleotide Array Sequence Analysisen_US
dc.subject.meshOrigin Recognition Complex - Genetics - Metabolismen_US
dc.subject.meshRna Interferenceen_US
dc.subject.meshRna, Small Interfering - Geneticsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshX Chromosome Inactivation - Physiologyen_US
dc.titleDiverse factors are involved in maintaining X chromosome inactivationen_US
dc.typeArticleen_US
dc.identifier.emailChan, KM: ming616@graduate.hku.hken_US
dc.identifier.authorityChan, KM=rp01757en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.1107616108en_US
dc.identifier.pmid21940502-
dc.identifier.scopuseid_2-s2.0-80053641497en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80053641497&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume108en_US
dc.identifier.issue40en_US
dc.identifier.spage16699en_US
dc.identifier.epage16704en_US
dc.identifier.isiWOS:000295536000046-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChan, KM=8631854500en_US
dc.identifier.scopusauthoridZhang, H=55685682000en_US
dc.identifier.scopusauthoridMalureanu, L=8263040000en_US
dc.identifier.scopusauthoridVan Deursen, J=7003980379en_US
dc.identifier.scopusauthoridZhang, Z=35239002800en_US

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