Imbalanced chromatin distribution in cellular senescence specifies paraspeckle dynamics.

Abstract

Cellular senescence is accompanied by extensive genomic reorganization, such as senescence-associated heterochromatin foci and expanded interchromatin compartments, to ultimately affect gene expression. Here, we demonstrate that chromatin structural changes in senescent cells drive significant alterations in the phase behavior and motility of paraspeckles, a type of interchromatin compartment condensate. We observe increased numbers, size, and elongation of paraspeckles harboring NONO and NEAT1_2, driven by elevated levels of those components, consistent with the micellization model of longitudinal growth rather than condensate coalescence. Enhanced paraspeckle motility is associated with HP1α-mediated heterochromatin condensation and interchromatin expansion found in cellular senescence.