May the force be with you: Nuclear condensates function beyond transcription control

Abstract

Over the past decade, research has revealed biomolecular condensates' relevance in diverse cellular functions. Through a phase separation process, they concentrate macromolecules in subcompartments shaping the cellular organization and physiology. In the nucleus, biomolecular condensates assemble relevant biomolecules that orchestrate gene expression. We here hypothesize that chromatin condensates can also modulate the nongenetic functions of the genome, including the nuclear mechanical properties. The importance of chromatin condensates is supported by the genetic evidence indicating that mutations in their members are causative of a group of rare Mendelian diseases named chromatinopathies (CPs). Despite a broad spectrum of clinical features and the perturbations of the epigenetic machinery characterizing the CPs, recent findings highlighted negligible changes in gene expression. These data argue in favor of possible noncanonical functions of chromatin condensates in regulating the genome's spatial organization and, consequently, the nuclear mechanics. In this review, we discuss how condensates may impact nuclear mechanical properties, thus affecting the cellular response to mechanical cues and, eventually, cell fate and identity.Chromatin condensates organize macromolecules in the nucleus orchestrating the transcription regulation and mutations in their members are responsible for rare diseases named chromatinopathies. We argue that chromatin condensates, in concert with the nuclear lamina, may also govern the nuclear mechanical properties affecting the cellular response to external cues.

Coupling of Perinuclear Actin Cap and Nuclear Mechanics in Regulating Flow‐Induced Yap Spatiotemporal Nucleocytoplasmic Transport

“…To further validate the formation of actin cap, we performed Nesprin 1 staining, [ 13 ] a component of the LINC complex, and also observed a gradual increase in the frequency of Nesprin line‐positive nuclei with prolonged exposure to unidirectional shear stress (Figure S2c , Supporting Information). Considering the connection between nuclear stiffness and chromatin compaction, [ 14 ] we employed Brillouin microscopy for label‐free and contact‐free measurements of nuclear stiffness (Figure 1d ; Figure S4a , Supporting Information). The results show the increased nuclear stiffness under both unidirectional conditions with flow time (Figure 1e ; Figure S3d , Supporting Information).…”