A high-resolution view of transcription and chromatin states across distinct metabolic states in budding yeast

Under continuous, glucose-limited conditions, budding yeast exhibit robust metabolic cycles associated with major oscillations of gene expression and metabolic state. However, how such fluctuations might be coordinately linked to changes in chromatin status is less well understood. Here, we examine the correlated genome-wide transcription and chromatin states across the yeast metabolic cycle (YMC) at unprecedented temporal resolution, revealing a "just in time supply chain" by which specific cellular processes such as ribosome biogenesis are coordinated in time with remarkable precision. We identify distinct chromatin and splicing patterns associated with different gene categories and determine the relative timing of chromatin modifications to maximal transcription. Additionally, we interrogate chromatin modifier occupancy and observe subtly distinct spatial and temporal patterns compared to the modifications themselves. Furthermore, we identify multiple lysine mutants in H3 or H4 tails that disrupt metabolic cycling, supporting a potentially cooperative role of histone modifications in the YMC. Overall design: 16 time points RNA-seq and ChIP-seq of 8 histone marks over one metabolic cycle, 14 time points ChIP-seq of 3 chromatin modifiers over one metabolic cycle

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Kuang Z, Cai L, Zhang X, Ji H, Tu BP, Boeke JD