Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-Depleted Murine Embryonic Stem Cells

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Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-Depleted Murine Embryonic Stem Cells

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dc.contributor.author Airoldi, Edoardo Maria
dc.contributor.author Markowetz, Florian
dc.contributor.author Mulder, Klaas
dc.contributor.author Lemischka, Ihor
dc.contributor.author Troyanskaya, Olga
dc.date.accessioned 2011-09-15T23:38:21Z
dc.date.issued 2010
dc.identifier.citation Markowetz, Florian, Klaas W. Mulder, Edoardo M. Airoldi, Ihor R. Lemischka, and Olga G. Troyanskaya. 2010. Mapping dynamic histone acetylation patterns to gene expression in Nanog-depleted murine embryonic stem cells. PLoS Computational Biology 6(12): e1001034. en_US
dc.identifier.issn 1553-734X en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5132919
dc.description.abstract Embryonic 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. en_US
dc.description.sponsorship Statistics en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pcbi.1001034 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002996/ en_US
dash.license OAP
dc.title Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-Depleted Murine Embryonic Stem Cells en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Computational Biology en_US
dash.depositing.author Airoldi, Edoardo Maria
dc.date.available 2011-09-15T23:38:21Z

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  • FAS Scholarly Articles [7262]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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