Cell cycle arrest explained the observed bulk 3D genomic alterations in response to long term heat shock for mammalian cells

Heat shock is a common environmental stress, while the response of the nucleus to it remains controversial in mammalian cells. Acute reaction and chronic adaptation to environmental stress may have distinct internal rewiring in the gene regulation networks. However, this difference remains largely unexplored. Here, we report that chromatin conformation and chromatin accessibility respond differently in short- and long-term heat shock in human K562 cells. Interestingly, we found that chromatin conformation in K562 cells was largely stable in response to short heat shock, while showed clear and characteristic changes after long-term heat treatment with little alteration in chromatin accessibility during the whole process. We further showed in silico and experimental evidence strongly suggesting that changes in chromatin conformation may largely stem from an accumulation of cells in the M stage of cell cycle in response to heat shock. Our results represent a paradigm shift away from the controversial view of chromatin response to heat shock and emphasize the necessity of cell cycle analysis while when interpreting bulk Hi-C data.