High resolution chromatin dynamics during a yeast stress response

Covalent histone modifications are highly conserved and play multiple roles in eukaryotic transcription regulation. Because of extensive crosstalk between transcriptional processes and histone modifications, steady state observations are insufficient to fully disentangle histone modification networks. As transient perturbation of feedback mechanisms can reveal network structure, we mapped 26 histone modifications genome-wide over a time course following dramatic transcriptional reprogramming – response to diamide stress in yeast. Interestingly, while we observed limited combinatorial complexity in steady-state histone modification patterns, consistent with previous studies, the combinatorial complexity of histone modification space increased modestly during the stress response, resulting from roughly 3% of nucleosomes transiently populating rare histone modification states. We show that most of these short-lived histone mark combinations result from differences in histone modification dynamics that transiently uncouple highly correlated marks, with slow histone methylation changes often lagging the more rapid changes in acetylation. Together, our results provide the first detailed view of an epigenome in transition. Overall design: Mnase-ChIP-Seq with 26 antibodies, throuh a diamide stress response (0,4,8,15,30,60 minutes). Performed in batches, in each batch the MNase input is also sequenced in each time point.