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Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.

cam.issuedOnline2018-10-25
dc.contributor.authorKazachenka, Anastasiya
dc.contributor.authorBertozzi, Tessa M
dc.contributor.authorSjoberg-Herrera, Marcela K
dc.contributor.authorWalker, Nic
dc.contributor.authorGardner, Joseph
dc.contributor.authorGunning, Richard
dc.contributor.authorPahita, Elena
dc.contributor.authorAdams, Sarah
dc.contributor.authorAdams, David
dc.contributor.authorFerguson-Smith, Anne C
dc.contributor.orcidFerguson-Smith, Anne [0000-0003-4996-9990]
dc.date.accessioned2018-11-22T00:31:38Z
dc.date.available2018-11-22T00:31:38Z
dc.date.issued2018-11-15
dc.description.abstractGenerally repressed by epigenetic mechanisms, retrotransposons represent around 40% of the murine genome. At the Agouti viable yellow (Avy) locus, an endogenous retrovirus (ERV) of the intracisternal A particle (IAP) class retrotransposed upstream of the agouti coat-color locus, providing an alternative promoter that is variably DNA methylated in genetically identical individuals. This results in variable expressivity of coat color that is inherited transgenerationally. Here, a systematic genome-wide screen identifies multiple C57BL/6J murine IAPs with Avy epigenetic properties. Each exhibits a stable methylation state within an individual but varies between individuals. Only in rare instances do they act as promoters controlling adjacent gene expression. Their methylation state is locus-specific within an individual, and their flanking regions are enriched for CTCF. Variably methylated IAPs are reprogrammed after fertilization and re-established as variable loci in the next generation, indicating reconstruction of metastable epigenetic states and challenging the generalizability of non-genetic inheritance at these regions.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32982
dc.identifier.eissn1097-4172
dc.identifier.issn0092-8674
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285629
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.cell.2018.09.043
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAgouti Signaling Protein
dc.subjectAnimals
dc.subjectBinding Sites
dc.subjectCCCTC-Binding Factor
dc.subjectDNA Methylation
dc.subjectEpigenesis, Genetic
dc.subjectGenes, Intracisternal A-Particle
dc.subjectGenetic Loci
dc.subjectGenome
dc.subjectGenomic Instability
dc.subjectHeredity
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectProtein Binding
dc.subjectRetroelements
dc.subjectTranscription, Genetic
dc.titleIdentification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.
dc.typeArticle
dcterms.dateAccepted2018-09-19
prism.endingPage1271.e13
prism.issueIdentifier5
prism.publicationDate2018
prism.publicationNameCell
prism.startingPage1259
prism.volume175
pubs.funder-project-idMedical Research Council (MR/J001597/1)
pubs.funder-project-idWellcome Trust (086838/Z/08/Z)
pubs.funder-project-idWellcome Trust (095606/Z/11/Z)
rioxxterms.licenseref.startdate2018-11
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.cell.2018.09.043

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