Saha Dhurjhoti, Animireddy Srinivas, Bartholomew Blaine
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, U.S.A.
Biochem Soc Trans. 2024 Apr 24;52(2):603-616. doi: 10.1042/BST20230416.
ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins. In development, SWI/SNF orchestrates the precise activation and repression of genes at different stages, safe guards the formation of specific cell lineages and tissues. Dysregulation of SWI/SNF have been implicated in diseases such as cancer, where they can drive uncontrolled cell proliferation and tumor metastasis. Additionally, SWI/SNF defects are associated with neurodevelopmental disorders, leading to disruption of neural development and function. This review offers insights into recent developments regarding the roles of the SWI/SNF complex in pluripotency and cell lineage primining and the approaches that have helped delineate its importance. Understanding these molecular mechanisms is crucial for unraveling the intricate processes governing embryonic stem cell biology and developmental transitions and may potentially apply to human diseases linked to mutations in the SWI/SNF complex.
ATP 依赖性染色质重塑因子在转录、DNA 复制与修复以及维持基因组完整性方面发挥着关键作用。SWI/SNF 重塑因子最初是在酵母基因筛选中被发现的,筛选的是参与交配型转换或使用替代能源的因子,因此被称为 SWI/SNF 复合物(SWItch/Sucrose NonFermentable 的缩写)。SWI/SNF 复合物利用 ATP 水解产生的能量来破坏组蛋白 - DNA 相互作用,并移动、排出或重新定位核小体,使潜在的 DNA 更容易被特定转录因子和其他调节蛋白所接近。在发育过程中,SWI/SNF 协调不同阶段基因的精确激活和抑制,保障特定细胞谱系和组织的形成。SWI/SNF 的失调与癌症等疾病有关,在癌症中它们可驱动细胞的不受控制增殖和肿瘤转移。此外,SWI/SNF 缺陷与神经发育障碍有关,导致神经发育和功能的破坏。本综述提供了关于 SWI/SNF 复合物在多能性和细胞谱系启动中的作用的最新进展以及有助于阐明其重要性的方法的见解。了解这些分子机制对于揭示控制胚胎干细胞生物学和发育转变的复杂过程至关重要,并且可能适用于与 SWI/SNF 复合物突变相关的人类疾病。