Microtubule Assists Actomyosin to Regulate Cell Nuclear Mechanics and Chromatin Accessibility  

作　　者：Jiwen Geng Zhefeng Kang Qian Sun Man Zhang Peng Wang Yupei Li Jiameng Li Baihai Su Qiang Wei 

机构地区：[1]Department of Nephrology,West China Hospital,Sichuan University,Chengdu,610041,China [2]College of Polymer Science and Engineering,College of Biomedical Engineering,State Key Laboratory of Polymer Materials and Engineering Sichuan University,Chengdu,610065,China [3]Department of Cardiovascular Surgery,West China Hospital,Sichuan University,Chengdu,610041,China

出　　处：《Research》2023年第3期619-631,共13页研究（英文）

基　　金：the National Natural Science Foundation of China(Grant No.32000951,51973129);the Sichuan Science and Technology Program(Grant No.2022YFS0147);the Science and Technology Achievement Transformation Fund of West China Hospital of Sichuan University(Grant No.CGZH19006);the Med-X Innovation Programme of Med-X Center for Materials of Sichuan University(Grant No.MCM202101);the 1.3.5 project for disciplines of excellence from West China Hospital of Sichuan University(Grant No.ZYJC21010);Med+Biomaterial Institute of West China Hospital/West China School of Medicine of Sichuan University(Grant No.ZYME20001).

摘　　要：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.

关 键 词：determination behaviors STIFF 

分 类 号：O57[理学—粒子物理与原子核物理]