Summary
Transcriptional induction of Heat Shock Protein (HSP) genes is accompanied by dynamic changes in their 3D structure and spatial organization, yet the molecular basis for these striking phenomena remains unknown. Using chromosome conformation capture and single cell imaging, we show that Heat Shock Factor 1 (Hsf1)-activated genes in Saccharomyces cerevisiae rapidly and reversibly coalesce into intranuclear foci, while genes activated by Msn2 and Msn4, alternative thermal stress-responsive activators, do not. Likewise, constitutively expressed genes do not coalesce, even those interposed between HSP genes. Stress-activated Hsf1 coalesces into discrete subnuclear puncta, and in concert with its target HSP genes, de-coalesces and disperses into the nucleoplasm upon transcriptional attenuation. Hsf1 is both necessary and sufficient for driving gene coalescence, whereas RNA Pol II is necessary but not sufficient. Our findings reveal that gene coalescence is activator-dependent and refute models which posit that gene repositioning is a general feature of transcriptional activation.