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      A Compendium of Nucleosome and Transcript Profiles Reveals Determinants of Chromatin Architecture and Transcription

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          Nucleosomes in all eukaryotes examined to date adopt a characteristic architecture within genes and play fundamental roles in regulating transcription, yet the identity and precise roles of many of the trans-acting factors responsible for the establishment and maintenance of this organization remain to be identified. We profiled a compendium of 50 yeast strains carrying conditional alleles or complete deletions of genes involved in transcriptional regulation, histone biology, and chromatin remodeling, as well as compounds that target transcription and histone deacetylases, to assess their respective roles in nucleosome positioning and transcription. We find that nucleosome patterning in genes is affected by many factors, including the CAF-1 complex, Spt10, and Spt21, in addition to previously reported remodeler ATPases and histone chaperones. Disruption of these factors or reductions in histone levels led genic nucleosomes to assume positions more consistent with their intrinsic sequence preferences, with pronounced and specific shifts of the +1 nucleosome relative to the transcription start site. These shifts of +1 nucleosomes appear to have functional consequences, as several affected genes in Ino80 mutants exhibited altered expression responses. Our parallel expression profiling compendium revealed extensive transcription changes in intergenic and antisense regions, most of which occur in regions with altered nucleosome occupancy and positioning. We show that the nucleosome-excluding transcription factors Reb1, Abf1, Tbf1, and Rsc3 suppress cryptic transcripts at their target promoters, while a combined analysis of nucleosome and expression profiles identified 36 novel transcripts that are normally repressed by Tup1/Cyc8. Our data confirm and extend the roles of chromatin remodelers and chaperones as major determinants of genic nucleosome positioning, and these data provide a valuable resource for future studies.

          Author Summary

          The genome in eukaryotic cells is packaged into nucleosomes, which play critical roles in regulating where and when different genes are expressed. For example, nucleosomes can physically block access of transcription factor to sites on DNA or direct regulatory proteins to DNA. Consistent with these roles, nucleosomes assume a stereotypical pattern around genes: they are depleted at the promoter region that marks the start of genes and assume a regularly spaced array within genes. To identify factors involved in this organization, we generated high-resolution nucleosome and transcriptome maps for 50 loss-of-function mutants with known or suspected roles in nucleosome biology in budding yeast. We show that nucleosome organization is determined by the combined effects of many factors that often exert opposing forces on nucleosomes. We further demonstrate that specific nucleosomes can be positioned independently within genes and that repositioning of nucleosomes at the start of genes may affect expression of these genes in response to environmental stimuli. Data mining of this extensive resource allowed us to show that general transcription factors act as insulators at diverging promoters to prevent the formation of cryptic transcripts, and also revealed 36 novel transcripts regulated by the Tup1/Cyc8 complex.

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          Author and article information

          Role: Editor
          PLoS Genet
          PLoS Genet
          PLoS Genetics
          Public Library of Science (San Francisco, USA )
          May 2013
          May 2013
          2 May 2013
          : 9
          : 5
          [1 ]Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
          [2 ]Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada
          [3 ]Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada
          [4 ]Department of Medical Research, Banting and Best, Toronto, Ontario, Canada
          [5 ]Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada
          [6 ]Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
          Medical Research Council Human Genetics Unit, United Kingdom
          Author notes

          The authors have declared that no competing interests exist.

          Conceived and designed the experiments: CN HvB TRH. Performed the experiments: KT HvB MG SM. Analyzed the data: HvB. Contributed reagents/materials/analysis tools: CN TRH. Wrote the paper: HvB CN.


          This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

          Page count
          Pages: 18
          CN and TRH were supported by a grant from the Canadian Institutes for Health Research (CIHR; grant MOP-86705). HvB was supported by the Netherlands Organization for Scientific Research (NWO; grant 825.06.033) and the CIHR (grant 193588). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
          Research Article
          Gene Expression
          DNA transcription
          Gene Function
          Chromosome Biology
          Model Organisms
          Yeast and Fungal Models
          Saccharomyces Cerevisiae



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