Abstract
The eukaryotic genome is packaged as chromatin with nucleosomes comprising its basic structural unit, but the detailed structure of chromatin and its dynamic remodeling in terms of individual nucleosome positions has not been completely defined experimentally for any genome. We used ultra-high–throughput sequencing to map the remodeling of individual nucleosomes throughout the yeast genome before and after a physiological perturbation that causes genome-wide transcriptional changes. Nearly 80% of the genome is covered by positioned nucleosomes occurring in a limited number of stereotypical patterns in relation to transcribed regions and transcription factor binding sites. Chromatin remodeling in response to physiological perturbation was typically associated with the eviction, appearance, or repositioning of one or two nucleosomes in the promoter, rather than broader region-wide changes. Dynamic nucleosome remodeling tends to increase the accessibility of binding sites for transcription factors that mediate transcriptional changes. However, specific nucleosomal rearrangements were also evident at promoters even when there was no apparent transcriptional change, indicating that there is no simple, globally applicable relationship between chromatin remodeling and transcriptional activity. Our study provides a detailed, high-resolution, dynamic map of single-nucleosome remodeling across the yeast genome and its relation to global transcriptional changes.
Highlights
The eukaryotic genome is compacted into nucleosomal arrays composed of 146-bp DNA wrapped around a core histone octamer complex [1]
A fundamental aspect of genome packing is the spooling of DNA around nucleosomes—structures formed from histone proteins—which must be dislodged during transcription
We identified all the nucleosome displacements associated with a physiological perturbation causing genome-wide transcriptional changes in the eukaryote Saccharomyces cerevisiae
Summary
The eukaryotic genome is compacted into nucleosomal arrays composed of 146-bp DNA wrapped around a core histone octamer complex [1]. The location of nucleosomes affects nearly every cellular process requiring access to genomic DNA, but it is not well understood how nucleosomes are positioned and remodeled throughout any genome. Mapping nucleosome positions using DNA microarrays covering 4% of the yeast genome has shown that a majority of assayable nucleosomes were well positioned [2]. Computational analyses incorporating structural mechanics of nucleosome associated DNA [3,4,5] and comparative genetics [6] have predicted nucleosome positions in the yeast genome. Experimental validation and comparison with available in vivo data show that intrinsic signals in genomic DNA determine only 15%–17% of nucleosome positioning above what is expected by chance [3,4]. In vivo nucleosome positions are influenced by the presence of numerous ATPdependent remodelers, and the transcriptional machinery [7,8]
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