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dc.creatorMarkowetz, F
dc.creatorMulder, KW
dc.creatorAiroldi, EM
dc.creatorLemischka, IR
dc.creatorTroyanskaya, OG
dc.date.accessioned2021-01-31T23:51:46Z
dc.date.available2021-01-31T23:51:46Z
dc.date.issued2010-12-01
dc.identifier.issn1553-734X
dc.identifier.issn1553-7358
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/5515
dc.identifier.other21187909 (pubmed)
dc.identifier.urihttp://hdl.handle.net/20.500.12613/5533
dc.description.abstractEmbryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in a concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step toward dissecting the multilayer regulatory mechanisms that determine stem cell fate. © 2010 Markowetz et al.
dc.format.extente1001034-e1001034
dc.language.isoen
dc.relation.haspartPLoS Computational Biology
dc.relation.isreferencedbyPublic Library of Science (PLoS)
dc.rightsCC BY
dc.subjectAcetylation
dc.subjectAnimals
dc.subjectCluster Analysis
dc.subjectComputational Biology
dc.subjectEmbryonic Stem Cells
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation
dc.subjectGene Silencing
dc.subjectGenome-Wide Association Study
dc.subjectHistones
dc.subjectHomeodomain Proteins
dc.subjectMice
dc.subjectNanog Homeobox Protein
dc.subjectPhenotype
dc.titleMapping dynamic histone acetylation patterns to gene expression in nanog-depleted murine embryonic stem cells
dc.typeArticle
dc.type.genreJournal Article
dc.relation.doi10.1371/journal.pcbi.1001034
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.creator.orcidAiroldi, Edoardo|0000-0002-3512-0542
dc.date.updated2021-01-31T23:51:42Z
refterms.dateFOA2021-01-31T23:51:46Z


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