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Embryonic stem cells (ESC) have the potential to self-renew indefinitely andto differentiate into any of the three germ layers. The molecular mechanismsfor self-renewal, maintenance of pluripotency and lineage specification arepoorly understood, but recent results point to a key role for epigeneticmechanisms. In this study, we focus on quantifying the impact of histone 3acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. Weanalyze genome-wide histone acetylation patterns and gene expression profilesmeasured over the first five days of cell differentiation triggered bysilencing Nanog, a key transcription factor in ESC regulation. We explore thetemporal and spatial dynamics of histone acetylation data and its correlationwith gene expression using supervised and unsupervised statistical models. On agenome-wide scale, changes in acetylation are significantly correlated tochanges in mRNA expression and, surprisingly, this coherence increases overtime. We quantify the predictive power of histone acetylation for geneexpression changes in a balanced cross-validation procedure. In an in-depthstudy we focus on genes central to the regulatory network of Mouse ESC,including those identified in a recent genome-wide RNAi screen and in thePluriNet, a computationally derived stem cell signature. We find that comparedto the rest of the genome, ESC-specific genes show significantly moreacetylation signal and a much stronger decrease in acetylation over time, whichis often not reflected in an concordant expression change. These results shedlight on the complexity of the relationship between histone acetylation andgene expression and are a step forward to dissect the multilayer regulatorymechanisms that determine stem cell fate.

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