SWI/SNF (BAF)复合物:从框架到内皮机械转导的功能作用。

4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology
Current topics in membranes Pub Date : 2021-01-01 Epub Date: 2021-10-09 DOI:10.1016/bs.ctm.2021.09.006
Sandeep Kumar
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引用次数: 0

摘要

内皮细胞(ECs)由于位于血管腔内,因此经常受到一系列机械因素的影响,尤其是剪切应力。血流可以通过在转录组学、蛋白质组学、miRNomic、代谢组学和表观基因组水平上调节内皮过程,从而调节内皮生物学和病理生理学的各个方面。ECs通过机械传感和机械转导的特殊机制感知、响应和适应改变的血流模式和剪切剖面,从而导致其基因表达的定性和定量差异。染色质调节蛋白可以通过改变核小体启动子、增强子、沉默子、绝缘子和基因座控制区的组织来调节转录激活。最近的研究表明,SWI/SNF (SWItch/ sugar Non-Fermentable)或BRG1/BRM-associated factor (BAF)复合物调节DNA可及性和染色质结构。自发现以来,人们对与染色质重塑相关的BAF复合物的基因调控机制进行了深入研究,以探讨其在多种疾病表型中的作用。到目前为止,很明显:(1)SWI/SNF复合物广泛调节转录增强子的活性以控制谱系特异性分化;(2)BAF复合物蛋白的突变导致发育障碍和癌症。目前尚不清楚血流是否可以调节SWI/SNF复合物的活性来调节EC的分化和重编程。本文从结构和功能的角度强调SWI/SNF复合物的综合作用,并特别提到心血管疾病(cvd)。该综述还强调了如何通过血流调节这种复合物,从而发现治疗血管疾病中内皮功能障碍的新治疗干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SWI/SNF (BAF) complexes: From framework to a functional role in endothelial mechanotransduction.

Endothelial cells (ECs) are constantly subjected to an array of mechanical cues, especially shear stress, due to their luminal placement in the blood vessels. Blood flow can regulate various aspects of endothelial biology and pathophysiology by regulating the endothelial processes at the transcriptomic, proteomic, miRNomic, metabolomics, and epigenomic levels. ECs sense, respond, and adapt to altered blood flow patterns and shear profiles by specialized mechanisms of mechanosensing and mechanotransduction, resulting in qualitative and quantitative differences in their gene expression. Chromatin-regulatory proteins can regulate transcriptional activation by modifying the organization of nucleosomes at promoters, enhancers, silencers, insulators, and locus control regions. Recent research efforts have illustrated that SWI/SNF (SWItch/Sucrose Non-Fermentable) or BRG1/BRM-associated factor (BAF) complex regulates DNA accessibility and chromatin structure. Since the discovery, the gene-regulatory mechanisms of the BAF complex associated with chromatin remodeling have been intensively studied to investigate its role in diverse disease phenotypes. Thus far, it is evident that (1) the SWI/SNF complex broadly regulates the activity of transcriptional enhancers to control lineage-specific differentiation and (2) mutations in the BAF complex proteins lead to developmental disorders and cancers. It is unclear if blood flow can modulate the activity of SWI/SNF complex to regulate EC differentiation and reprogramming. This review emphasizes the integrative role of SWI/SNF complex from a structural and functional standpoint with a special reference to cardiovascular diseases (CVDs). The review also highlights how regulation of this complex by blood flow can lead to the discovery of new therapeutic interventions for the treatment of endothelial dysfunction in vascular diseases.

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来源期刊
Current topics in membranes
Current topics in membranes 生物-生化与分子生物学
CiteScore
3.50
自引率
0.00%
发文量
10
审稿时长
>12 weeks
期刊介绍: Current Topics in Membranes provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology.
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