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Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation.

Shivaswamy S, Bhinge A, Zhao Y, Jones S, Hirst M, Iyer VR - PLoS Biol. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, and Section of Molecular Genetics and Microbiology, University of Texas at Austin,Austin, Texas, United States of America.

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.

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Dynamic Nucleosome Remodeling Affects the Accessibility of Transcription Factor Binding Sites and the TSS(A) Example of nucleosome eviction at the heat-shock–activated UBC4 promoter (blue line). Nucleosomes defined by our sequencing data are indicated by ovals, colored according to their stability score. The positions of transcription factor binding sites are from [17] and are shaded according to their confidence. Binding sites for other transcription factors are also affected by remodeling (unpublished data), but these are not known to be related to heat shock.(B) Example of nucleosome appearance at the heat-shock–repressed RPL17B promoter (red line).
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pbio-0060065-g005: Dynamic Nucleosome Remodeling Affects the Accessibility of Transcription Factor Binding Sites and the TSS(A) Example of nucleosome eviction at the heat-shock–activated UBC4 promoter (blue line). Nucleosomes defined by our sequencing data are indicated by ovals, colored according to their stability score. The positions of transcription factor binding sites are from [17] and are shaded according to their confidence. Binding sites for other transcription factors are also affected by remodeling (unpublished data), but these are not known to be related to heat shock.(B) Example of nucleosome appearance at the heat-shock–repressed RPL17B promoter (red line).

Mentions: Nucleosome positioning can influence the accessibility of the core promoter as well as binding sites for sequence-specific transcriptional regulators [10,26]. About 90% of the sites occupied by transcription factors on chromosome III under normal growth conditions were depleted of nucleosomes [2]. Examination of single-nucleosome remodeling at promoters that were activated or repressed by heat shock in our data revealed instances where the accessibility of the TSS and of experimentally defined transcription factor binding sites was indeed affected by remodeling. For example, at the UBC4 promoter, which is activated by heat shock, three moderately positioned nucleosomes covering two distinct Hsf1 binding sites as well as the TSS were evicted, whereas a single, well-positioned nucleosome appeared between the two Hsf1 binding sites (Figure 5A). Conversely, at the RPL17B promoter, which is repressed by heat shock, one well-positioned nucleosome appeared after heat shock to cover the TSS and a low-confidence proximal Rap1 binding site. Interestingly, another moderate nucleosome upstream was evicted, exposing a higher confidence distal Rap1 binding site as well as an Fhl1 site (Figure 5B). Such eviction and appearance of nucleosomes at adjacent sites could either reflect translational repositioning or independent events; our experiments cannot distinguish between these two possibilities.


Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation.

Shivaswamy S, Bhinge A, Zhao Y, Jones S, Hirst M, Iyer VR - PLoS Biol. (2008)

Dynamic Nucleosome Remodeling Affects the Accessibility of Transcription Factor Binding Sites and the TSS(A) Example of nucleosome eviction at the heat-shock–activated UBC4 promoter (blue line). Nucleosomes defined by our sequencing data are indicated by ovals, colored according to their stability score. The positions of transcription factor binding sites are from [17] and are shaded according to their confidence. Binding sites for other transcription factors are also affected by remodeling (unpublished data), but these are not known to be related to heat shock.(B) Example of nucleosome appearance at the heat-shock–repressed RPL17B promoter (red line).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2267817&req=5

pbio-0060065-g005: Dynamic Nucleosome Remodeling Affects the Accessibility of Transcription Factor Binding Sites and the TSS(A) Example of nucleosome eviction at the heat-shock–activated UBC4 promoter (blue line). Nucleosomes defined by our sequencing data are indicated by ovals, colored according to their stability score. The positions of transcription factor binding sites are from [17] and are shaded according to their confidence. Binding sites for other transcription factors are also affected by remodeling (unpublished data), but these are not known to be related to heat shock.(B) Example of nucleosome appearance at the heat-shock–repressed RPL17B promoter (red line).
Mentions: Nucleosome positioning can influence the accessibility of the core promoter as well as binding sites for sequence-specific transcriptional regulators [10,26]. About 90% of the sites occupied by transcription factors on chromosome III under normal growth conditions were depleted of nucleosomes [2]. Examination of single-nucleosome remodeling at promoters that were activated or repressed by heat shock in our data revealed instances where the accessibility of the TSS and of experimentally defined transcription factor binding sites was indeed affected by remodeling. For example, at the UBC4 promoter, which is activated by heat shock, three moderately positioned nucleosomes covering two distinct Hsf1 binding sites as well as the TSS were evicted, whereas a single, well-positioned nucleosome appeared between the two Hsf1 binding sites (Figure 5A). Conversely, at the RPL17B promoter, which is repressed by heat shock, one well-positioned nucleosome appeared after heat shock to cover the TSS and a low-confidence proximal Rap1 binding site. Interestingly, another moderate nucleosome upstream was evicted, exposing a higher confidence distal Rap1 binding site as well as an Fhl1 site (Figure 5B). Such eviction and appearance of nucleosomes at adjacent sites could either reflect translational repositioning or independent events; our experiments cannot distinguish between these two possibilities.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, and Section of Molecular Genetics and Microbiology, University of Texas at Austin,Austin, Texas, United States of America.

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.

Show MeSH
Related in: MedlinePlus