PT  - JOURNAL ARTICLE
AU  - Ray, Judhajeet
AU  - Munn, Paul R.
AU  - Vihervaara, Anniina
AU  - Lewis, James J.
AU  - Ozer, Abdullah
AU  - Danko, Charles G.
AU  - Lis, John T.
TI  - Chromatin conformation remains stable upon extensive transcriptional changes driven by heat shock
AID  - 10.1073/pnas.1901244116
DP  - 2019 Sep 24
TA  - Proceedings of the National Academy of Sciences
PG  - 19431--19439
VI  - 116
IP  - 39
4099  - http://www.pnas.org/content/116/39/19431.short
4100  - http://www.pnas.org/content/116/39/19431.full
SO  - Proc Natl Acad Sci USA2019 Sep 24; 116
AB  - Dramatic and rapid changes in transcription take place upon heat shock (HS), where thousands of genes have been shown to be immediately up- or down-regulated in metazoans. The role of large-scale chromatin conformation and changes in long-range interactions between distal regulatory elements and HS-regulated promoters remains unclear. Our study shows that topologically associating domains and compartment structures remain remarkably unchanged upon acute HS in human and Drosophila, while only modest changes of distal regulatory interactions are observed in human cells. These results suggest that the global chromatin structure required for the HS response is preestablished across metazoans in order to drive transcriptional changes in HS responsive genes.Heat shock (HS) initiates rapid, extensive, and evolutionarily conserved changes in transcription that are accompanied by chromatin decondensation and nucleosome loss at HS loci. Here we have employed in situ Hi-C to determine how heat stress affects long-range chromatin conformation in human and Drosophila cells. We found that compartments and topologically associating domains (TADs) remain unchanged by an acute HS. Knockdown of Heat Shock Factor 1 (HSF1), the master transcriptional regulator of the HS response, identified HSF1-dependent genes and revealed that up-regulation is often mediated by distal HSF1 bound enhancers. HSF1-dependent genes were usually found in the same TAD as the nearest HSF1 binding site. Although most interactions between HSF1 binding sites and target promoters were established in the nonheat shock (NHS) condition, a subset increased contact frequency following HS. Integrating information about HSF1 binding strength, RNA polymerase abundance at the HSF1 bound sites (putative enhancers), and contact frequency with a target promoter accurately predicted which up-regulated genes were direct targets of HSF1 during HS. Our results suggest that the chromatin conformation necessary for a robust HS response is preestablished in NHS cells of diverse metazoan species.