Rappaport Research Institute and Faculty of Medicine, The Rappaport Faculty of Medicine Technion-IIT, Technion Integrative Cancer Center (TICC), Technion-Israel Institute of Technology, Bat-Galim, 3109610, Haifa, Israel.
Cell Mol Life Sci. 2021 Apr;78(7):3141-3158. doi: 10.1007/s00018-020-03731-4. Epub 2021 Jan 28.
Regulation of the differentiated identity requires active and continued supervision. Inability to maintain the differentiated state is a hallmark of aging and aging-related disease. To maintain cellular identity, a network of nuclear regulators is devoted to silencing previous and non-relevant gene programs. This network involves transcription factors, epigenetic regulators, and the localization of silent genes to heterochromatin. Together, identity supervisors mold and maintain the unique nuclear environment of the differentiated cell. This review describes recent discoveries regarding mechanisms and regulators that supervise the differentiated identity and protect from de-differentiation, tumorigenesis, and attenuate forced somatic cell reprograming. The review focuses on mechanisms involved in H3K9me3-decorated heterochromatin and the importance of nuclear lamins in cell identity. We outline how the biophysical properties of these factors are involved in self-compartmentalization of heterochromatin and cell identity. Finally, we discuss the relevance of these regulators to aging and age-related disease.
调控分化状态需要积极且持续的监督。无法维持分化状态是衰老和与衰老相关疾病的标志。为了维持细胞身份，一个核调控网络致力于沉默先前的和不相关的基因程序。该网络涉及转录因子、表观遗传调控因子，以及将沉默基因定位到异染色质。这些身份监督者共同塑造和维持分化细胞的独特核环境。这篇综述描述了关于监督分化状态的机制和调节因子的最新发现，这些机制和调节因子可以防止去分化、肿瘤发生，并减弱强制体细胞重编程。综述重点介绍了 H3K9me3 修饰的异染色质和核纤层蛋白在细胞身份中的重要性涉及的机制。我们概述了这些因素的物理特性如何参与异染色质和细胞身份的自我分隔。最后，我们讨论了这些调节因子与衰老和与衰老相关疾病的相关性。
