Primordial super-enhancers: heat shock-induced chromatin organization in yeast.

Specialized mechanisms ensure proper expression of critically important genes such as those specifying cell identity or conferring protection from environmental stress. Investigations of the heat shock response have been critical in elucidating basic concepts of transcriptional control. Recent studies demonstrate that in response to thermal stress, heat shock-responsive genes associate with high levels of transcriptional activators and coactivators and those in yeast intensely interact across and between chromosomes, coalescing into condensates. In mammalian cells, cell identity genes that are regulated by super-enhancers (SEs) are also densely occupied by transcriptional machinery that form phase-separated condensates. We suggest that the stress-remodeled yeast nucleome bears functional and structural resemblance to mammalian SEs, and will reveal fundamental mechanisms of gene control by transcriptional condensates. The rapid dynamics, robust induction, and conserved components of the HSF1-driven heat shock response make it an ideal system to study eukaryotic gene regulation. Heat shock (acute thermal stress) induces both short- and long-range changes in the chromosomal topology of budding yeast Heat Shock Protein (HSP) genes, culminating in their physical coalescence. HSP gene coalescence shares several key attributes with mammalian super-enhancers and multi-enhancer olfactory receptor hubs, including exceptional concentration of transcription factors and coactivators, extensive DNA looping and clustering, and cooperative assembly into phase-separated condensates. Elucidating the molecular basis for HSP gene coalescence could reveal fundamental mechanisms of gene control during critical cellular processes such as differentiation and development. [ABSTRACT FROM AUTHOR]