The effect of microgravity and flows on the organization and dynamics of the human genome

The human genome is highly organized and dynamic across different length scales. Genome organization and dynamics change upon exposure to mechanical stresses, leading to changes in transcription, replication, and DNA repair. Gravity presents a constant mechanical stress applied to the genome-in its absence, i.e., microgravity, gene expression markedly changes-yet the role of gravity in the genome's organization and function is unknown. Here, we investigate changes in the genome's organization and dynamics upon simulated microgravity and flows. We find that the nucleus changes its shape and size, with liquid phases inside the nucleus, such as nucleolus, visibly affected by the lack of buoyancy and convection in the nucleoplasm. Notably, the genome organization and dynamics remain largely preserved. While flows cause DNA damage, simulated microgravity does not. Our study provides fundamental biophysical insights into the nuclear and genome organization, highlighting its robustness against mechanical stresses and revealing key aspects of the role of gravity in the cell.