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dc.contributor.authorLee, Hangnohen
dc.contributor.authorCho, Dong-Yeonen
dc.contributor.authorWojtowicz, Damianen
dc.contributor.authorHarbison, Susan Ten
dc.contributor.authorRussell, Steveen
dc.contributor.authorOliver, Brianen
dc.contributor.authorPrzytycka, Teresa Men
dc.date.accessioned2018-04-20T14:13:17Z
dc.date.available2018-04-20T14:13:17Z
dc.date.issued2018-02-02en
dc.identifier.issn2160-1836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/275082
dc.description.abstractDNA copy number variation is associated with many high phenotypic heterogeneity disorders. We systematically examined the impact of Drosophila melanogaster deletions on gene expression profiles to ask whether increased expression variability owing to reduced gene dose might underlie this phenotypic heterogeneity. Indeed, we found that one-dose genes have higher gene expression variability relative to two-dose genes. We then asked whether this increase in variability could be explained by intrinsic noise within cells due to stochastic biochemical events, or whether expression variability is due to extrinsic noise arising from more complex interactions. Our modeling showed that intrinsic gene expression noise aver- ages at the organism level and thus cannot explain increased variation in one-dose gene expression. Interestingly, expression variability was related to the magnitude of expression compensation, suggesting that regulation, induced by gene dose reduction, is noisy. In a remarkable exception to this rule, the single X chromosome of males showed reduced expression variability, even compared with two-dose genes. Analysis of sex-transformed flies indicates that X expression variability is independent of the male differen- tiation program. Instead, we uncovered a correlation between occupancy of the chromatin-modifying pro- tein encoded by males absent on the first (mof) and expression variability, linking noise suppression to the specialized X chromosome dosage compensation system. MOF occupancy on autosomes in both sexes also lowered transcriptional noise. Our results demonstrate that gene dose reduction can lead to heterogeneous responses, which are often noisy. This has implications for understanding gene network regulatory interac- tions and phenotypic heterogeneity. Additionally, chromatin modification appears to play a role in damp- ening transcriptional noise.
dc.format.mediumElectronicen
dc.languageengen
dc.publisherGenetics Society of America
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectX Chromosomeen
dc.subjectChromatinen
dc.subjectAnimalsen
dc.subjectDrosophila melanogasteren
dc.subjectDrosophila Proteinsen
dc.subjectStochastic Processesen
dc.subjectGene Expression Profilingen
dc.subjectGene Dosageen
dc.subjectDosage Compensation, Geneticen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectDNA Copy Number Variationsen
dc.titleDosage-Dependent Expression Variation Suppressed on the Drosophila Male X Chromosome.en
dc.typeArticle
prism.endingPage598
prism.issueIdentifier2en
prism.publicationDate2018en
prism.publicationNameG3 (Bethesda, Md.)en
prism.startingPage587
prism.volume8en
dc.identifier.doi10.17863/CAM.22261
dcterms.dateAccepted2017-12-01en
rioxxterms.versionofrecord10.1534/g3.117.300400en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-02-02en
dc.contributor.orcidLee, Hangnoh [0000-0003-0442-8330]
dc.contributor.orcidWojtowicz, Damian [0000-0002-4274-6383]
dc.contributor.orcidRussell, Steven [0000-0003-0546-3031]
dc.contributor.orcidOliver, Brian [0000-0002-3455-4891]
dc.contributor.orcidPrzytycka, Teresa M [0000-0002-6261-277X]
dc.identifier.eissn2160-1836
rioxxterms.typeJournal Article/Reviewen


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International