Lung Diseases and Functional Epigenomics Laboratory (LUDIFE), Biomedicine Research Unit (UBIMED), Facultad de Estudios Superiores-Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM), Avenida de los Barrios #1, Colonia Los Reyes Iztacala, Tlalnepantla de Baz, 54090, Estado de México, México.
Departments of Pathology & Medical Biology and Pulmonology, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, 9713 Groningen, the Netherlands.
Mol Ther. 2024 Aug 7;32(8):2470-2488. doi: 10.1016/j.ymthe.2024.06.026. Epub 2024 Jun 22.
The SWI/SNF complex, also known as the BRG1/BRM-associated factor (BAF) complex, represents a critical regulator of chromatin remodeling mechanisms in mammals. It is alternatively referred to as mSWI/SNF and has been suggested to be imbalanced in human disease compared with human health. Three types of BAF assemblies associated with it have been described, including (1) canonical BAF (cBAF), (2) polybromo-associated BAF (PBAF), and (3) non-canonical BAF (ncBAF) complexes. Each of these BAF assemblies plays a role, either functional or dysfunctional, in governing gene expression patterns, cellular processes, epigenetic mechanisms, and biological processes. Recent evidence increasingly links the dysregulation of mSWI/SNF complexes to various human non-malignant lung chronic disorders and lung malignant diseases. This review aims to provide a comprehensive general state-of-the-art and a profound examination of the current understanding of mSWI/SNF assembly processes, as well as the structural and functional organization of mSWI/SNF complexes and their subunits. In addition, it explores their intricate functional connections with potentially dysregulated transcription factors, placing particular emphasis on molecular and cellular pathogenic processes in lung diseases. These processes are reflected in human epigenome aberrations that impact clinical and therapeutic levels, suggesting novel perspectives on the diagnosis and molecular therapies for human respiratory diseases.
SWI/SNF 复合物,也称为 BRG1/BRM 相关因子 (BAF) 复合物,是哺乳动物染色质重塑机制的关键调节剂。它也被称为 mSWI/SNF,与人类健康相比,在人类疾病中被认为是失衡的。已经描述了与之相关的三种 BAF 组装类型,包括 (1) 典型 BAF (cBAF)、(2) 多溴相关 BAF (PBAF) 和 (3) 非典型 BAF (ncBAF) 复合物。这些 BAF 组装中的每一种都在调节基因表达模式、细胞过程、表观遗传机制和生物学过程方面发挥着功能或功能失调的作用。最近的证据越来越多地将 mSWI/SNF 复合物的失调与各种人类非恶性肺慢性疾病和肺恶性疾病联系起来。本综述旨在提供对 mSWI/SNF 组装过程以及 mSWI/SNF 复合物及其亚基的结构和功能组织的全面深入的最新认识。此外,它还探讨了它们与潜在失调转录因子的复杂功能联系,特别强调了肺部疾病中的分子和细胞发病机制。这些过程反映在人类表观基因组的异常中,这些异常影响临床和治疗水平,为人类呼吸道疾病的诊断和分子治疗提供了新的视角。