BAF（mSWI/SNF）和PBAF复合物在癌症中的多种作用
The Many Roles of BAF (mSWI/SNF) and PBAF Complexes in Cancer.
作者信息
Hodges Courtney, Kirkland Jacob G, Crabtree Gerald R
机构信息
Departments of Pathology, Developmental Biology, and Genetics, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305.
出版信息
Cold Spring Harb Perspect Med. 2016 Aug 1;6(8):a026930. doi: 10.1101/cshperspect.a026930.
During the last decade, a host of epigenetic mechanisms were found to contribute to cancer and other human diseases. Several genomic studies have revealed that ∼20% of malignancies have alterations of the subunits of polymorphic BRG-/BRM-associated factor (BAF) and Polybromo-associated BAF (PBAF) complexes, making them among the most frequently mutated complexes in cancer. Recurrent mutations arise in genes encoding several BAF/PBAF subunits, including ARID1A, ARID2, PBRM1, SMARCA4, and SMARCB1 These subunits share some degree of conservation with subunits from related adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in model organisms, in which a large body of work provides insight into their roles in cancer. Here, we review the roles of BAF- and PBAF-like complexes in these organisms, and relate these findings to recent discoveries in cancer epigenomics. We review several roles of BAF and PBAF complexes in cancer, including transcriptional regulation, DNA repair, and regulation of chromatin architecture and topology. More recent results highlight the need for new techniques to study these complexes.
在过去十年中，人们发现许多表观遗传机制与癌症及其他人类疾病有关。多项基因组研究表明，约20%的恶性肿瘤存在多态性BRG-/BRM相关因子（BAF）和多溴相关BAF（PBAF）复合物亚基的改变，这使其成为癌症中最常发生突变的复合物之一。编码多个BAF/PBAF亚基的基因会反复发生突变，包括ARID1A、ARID2、PBRM1、SMARCA4和SMARCB1。这些亚基与模式生物中相关的三磷酸腺苷（ATP）依赖性染色质重塑复合物的亚基有一定程度的保守性，在模式生物中有大量研究深入探讨了它们在癌症中的作用。在这里，我们综述了BAF和PBAF样复合物在这些生物中的作用，并将这些发现与癌症表观基因组学的最新发现联系起来。我们回顾了BAF和PBAF复合物在癌症中的几种作用，包括转录调控、DNA修复以及染色质结构和拓扑结构的调控。最近的研究结果凸显了研究这些复合物需要新技术。
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