Biology Department, University of Massachusetts Amherst, Amherst, MA 01003, USA.
Molecular and Cellular Biology, University of Massachusetts Amherst, Amherst, MA 01003, USA.
J Cell Sci. 2023 Oct 15;136(20). doi: 10.1242/jcs.261547. Epub 2023 Oct 27.
Chromatin plays an essential role in the nuclear mechanical response and determining nuclear shape, which maintain nuclear compartmentalization and function. However, major genomic functions, such as transcription activity, might also impact cell nuclear shape via blebbing and rupture through their effects on chromatin structure and dynamics. To test this idea, we inhibited transcription with several RNA polymerase II inhibitors in wild-type cells and perturbed cells that presented increased nuclear blebbing. Transcription inhibition suppressed nuclear blebbing for several cell types, nuclear perturbations and transcription inhibitors. Furthermore, transcription inhibition suppressed nuclear bleb formation, bleb stabilization and bleb-based nuclear ruptures. Interestingly, transcription inhibition did not alter the histone H3 lysine 9 (H3K9) modification state, nuclear rigidity, and actin compression and contraction, which typically control nuclear blebbing. Polymer simulations suggested that RNA polymerase II motor activity within chromatin could drive chromatin motions that deform the nuclear periphery. Our data provide evidence that transcription inhibition suppresses nuclear blebbing and rupture, in a manner separate and distinct from chromatin rigidity.
染色质在核力学响应和确定核形状中起着至关重要的作用，核形状维持核区室化和功能。然而，主要的基因组功能，如转录活性，也可能通过影响染色质结构和动力学来影响核形状，导致泡状和破裂。为了验证这一观点，我们在野生型细胞和呈现出增加核泡状的扰动细胞中用几种 RNA 聚合酶 II 抑制剂抑制转录。转录抑制抑制了几种细胞类型的核泡状、核扰动和转录抑制剂的核泡状。此外，转录抑制抑制核泡形成、泡稳定和基于泡的核破裂。有趣的是，转录抑制并没有改变组蛋白 H3 赖氨酸 9（H3K9）修饰状态、核刚性以及通常控制核泡状的肌动蛋白压缩和收缩。聚合物模拟表明，染色质内的 RNA 聚合酶 II 马达活性可以驱动使核边缘变形的染色质运动。我们的数据提供了证据，表明转录抑制以一种与染色质刚性分开且不同的方式抑制核泡状和破裂。
