Nucleosome Repositioning Underlies Gene Expression Dynamics

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Nucleosome repositioning at gene promoters is a fundamental aspect of the regulation of gene expression. Yet the extent to which nucleosome repositioning is utilized within eukaryotic genomes is poorly understood. Here we report a comprehensive analysis of nucleosome positions as budding yeast transit through an ultradian cycle in which expression of >50% of all genes is highly synchronized. We present evidence of extensive nucleosome repositioning at thousands of gene promoters as genes are activated and repressed. During activation, nucleosomes are relocated to allow sites of general transcription factor binding and transcription initiation to become accessible. The extent of nucleosome shifting is closely related to the dynamic range of gene transcription and generally related to DNA sequence properties and use of the co- activators TFIID or SAGA. While nucleosome repositioning occurs pervasively, we find that a class of genes required for growth experience acute nucleosome shifting as cells enter the cell cycle. Significantly, our data identifies that the ATP-dependent chromatin-remodeling enzyme Snf2, plays a fundamental role in nucleosome repositioning and the expression of growth genes. Collectively our data and analysis provide a framework for understanding nucleosome dynamics in relation to fundamental DNA dependent transactions. Further, given the tight association between promoter nucleosomes and transcription initiation, we also investigated the relationship between transcription start site selection and nucleosome positioning. The data clearly demonstrate that the transition from promoter scanning to productive initiation by RNA polymerase is made upon invasion of the +1 nucleosome, and that transcripts initiating upstream of nucleosomes are targeted for rapid degradation.
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Budding Yeast; Chromatin; Nucleosome; Transcription; Yeast Metabolic Cycle; Yeast Respiratory Oscillation
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Molecular Biology
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Doctor of Philosophy
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Government Document
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Attribution-NonCommercial-NoDerivatives 4.0 International
dissertation or thesis
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