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.
摘要:
在过去的十年里,研究揭示了生物分子缩合物与不同细胞功能的相关性。通过相分离过程,它们将大分子集中在形成细胞组织和生理学的亚隔室中。在细胞核中,生物分子缩合物组装协调基因表达的相关生物分子。我们在这里假设染色质凝聚物也可以调节基因组的非遗传功能,包括核机械性能。染色质凝聚物的重要性得到遗传证据的支持,表明其成员中的突变是一组罕见的孟德尔疾病的病因,这些疾病被称为色素病(CPs)。尽管具有广泛的临床特征和表征CP的表观遗传机制的扰动,最近的发现强调了基因表达的可忽略的变化。这些数据支持染色质凝聚物在调节基因组的空间组织和可能的非规范功能,因此,核力学。在这次审查中,我们讨论了冷凝物如何影响核机械性能,从而影响细胞对机械线索的反应,最终,细胞命运和身份。染色质凝聚体在细胞核中组织大分子,协调转录调节,其成员中的突变是导致罕见疾病的原因。我们认为染色质凝聚,与核层一致,还可以控制影响细胞对外部线索反应的核机械性能。