Cellular behaviors and functions can be regulated by mechanical cues from microenvironments, which are transmitted to nucleus through the physical connections of cytoskeletons in the cells. How these physical connections determine transcriptional activity were not clearly known. The actomyosin, which generates intracellular traction force, has been recognized to control the nuclear morphology. Here, we have revealed that microtubule, the stiffest cytoskeleton, is also involved in the process of nuclear morphology alteration. The microtubule negatively regulates the actomyosin-induced nuclear invaginations but not the nuclear wrinkles. Moreover, these nuclear shape changes are proven to mediate the chromatin remodeling, which essentially mediates cell gene expression and phenotype determination. The actomyosin disruption leads to the loss of chromatin accessibility, which can be partly recovered by microtubule interference through nuclear shape control. This finding answers the question of how mechanical cues regulate chromatin accessibility and cell behaviors. It also provides new insights into cell mechanotransduction and nuclear mechanics.
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