Through the lens of phase separation: intrinsically unstructured protein and chromatin looping.

Through the lens of phase separation: intrinsically unstructured protein and chromatin looping.
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DOI:
10.1080/19491034.2023.2179766
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发表时间:
2023-12
期刊:
Nucleus (Austin, Tex.)
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三维(3D)染色质结构的建立、维持和动态调控为将基因组划分为功能独特的域提供了重要手段,这有助于定义与发育阶段和细胞类型相关的专门基因表达程序。越来越多的证据支持转录因子 (TF) 和染色质调节蛋白中隐藏的本质无序区域 (IDR) 在诱导相分离中发挥关键作用,相分离是一种通过生物分子的分配形成无膜冷凝物的现象。这一过程对于高阶染色质结构和循环的建立也至关重要。 IDR 和相分离驱动的 3D 基因组(重新)组织在癌症等疾病中经常出错。这篇综述讨论了理解本质无序蛋白 (IDP) 的相分离如何调节染色质循环和基因表达的最新进展。
The establishment, maintenance and dynamic regulation of three-dimensional (3D) chromatin structures provide an important means for partitioning of genome into functionally distinctive domains, which helps to define specialized gene expression programs associated with developmental stages and cell types. Increasing evidence supports critical roles for intrinsically disordered regions (IDRs) harbored within transcription factors (TFs) and chromatin-modulatory proteins in inducing phase separation, a phenomenon of forming membrane-less condensates through partitioning of biomolecules. Such a process is also critically involved in the establishment of high-order chromatin structures and looping. IDR- and phase separation-driven 3D genome (re)organization often goes wrong in disease such as cancer. This review discusses about recent advances in understanding how phase separation of intrinsically disordered proteins (IDPs) modulates chromatin looping and gene expression.
相位分离驱动异常的染色质循环和癌症发展。
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