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Nat Struct Mol Biol. 2014 Oct;21(10):854-63. doi: 10.1038/nsmb.2881. Epub 2014 Aug 31.

High-temporal-resolution view of transcription and chromatin states across distinct metabolic states in budding yeast.

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1] High Throughput Biology Center, Johns Hopkins University, Baltimore, Maryland, USA. [2] Department of Molecular Biology &Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [3] Institute for Systems Genetics, NYU Langone Medical Center, New York, New York, USA. [4] Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center, New York, New York, USA.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.


Under continuous, glucose-limited conditions, budding yeast exhibit robust metabolic cycles associated with major oscillations of gene expression. How such fluctuations are linked to changes in chromatin status is not well understood. Here we examine the correlated genome-wide transcription and chromatin states across the yeast metabolic cycle at unprecedented temporal resolution, revealing a 'just-in-time supply chain' by which components from specific cellular processes such as ribosome biogenesis become available in a highly coordinated manner. We identify distinct chromatin and splicing patterns associated with different gene categories and determine the relative timing of chromatin modifications relative to maximal transcription. There is unexpected variation in the chromatin modification and expression relationship, with histone acetylation peaks occurring with varying timing and 'sharpness' relative to RNA expression both within and between cycle phases. Chromatin-modifier occupancy reveals subtly distinct spatial and temporal patterns compared to those of the modifications themselves.

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