Abstract
The identification of nuclease-hypersensitive sites in an active globin gene1 and in the 5′ regions of fruit fly heat shock genes2 first suggested that chromatin changes accompany gene regulation in vivo. Here we present evidence that the basic repeating units of eukaryotic chromatin, nucleosomes, are depleted from active regulatory elements throughout the Saccharomyces cerevisiae genome in vivo. We found that during rapid mitotic growth, the level of nucleosome occupancy is inversely proportional to the transcriptional initiation rate at the promoter. We also observed a partial loss of histone H3 and H4 tetramers from the coding regions of the most heavily transcribed genes. Alterations in the global transcriptional program caused by heat shock or a change in carbon source resulted in an increased nucleosome occupancy at repressed promoters, and a decreased nucleosome occupancy at promoters that became active. Nuclease-hypersensitive sites occur in species from yeast to humans and result from chromatin perturbation3,4,5. Given the conservation of sequence and function among components of both chromatin and the transcriptional machinery, nucleosome depletion at promoters may be a fundamental feature of eukaryotic transcriptional regulation.
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Acknowledgements
We thank T. Petes, T. Magnuson, W. Marzluff and S. Henikoff for comments on the manuscript and K. Struhl for yeast strains. This work was supported by a National Human Genome Research Institute grant to J.D.L. and a National Institute of General Medical Sciences grant to B.D.S. B.D.S. is a Pew Scholar in the Biomedical Sciences.
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Lee, CK., Shibata, Y., Rao, B. et al. Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat Genet 36, 900–905 (2004). https://doi.org/10.1038/ng1400
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DOI: https://doi.org/10.1038/ng1400
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