Nagl Norman G, Wang Xiaomei, Patsialou Antonia, Van Scoy Michael, Moran Elizabeth
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
EMBO J. 2007 Feb 7;26(3):752-63. doi: 10.1038/sj.emboj.7601541. Epub 2007 Jan 25.
The mammalian SWI/SNF chromatin remodeling complex is becoming increasingly recognized for its role in tumor suppression, based on its ability to regulate accessibility of proliferation-associated genes to transcription factors. However, understanding the biological role of the complex is complicated because the same complex seemingly plays both positive and negative roles in gene expression. Work described here reveals that a choice between two independently encoded, closely related variants of a major subunit of the ARID protein family determines whether the SWI/SNF complex forms further associations with activator versus repressor complexes. The choice distinguishes assemblies with opposite effects on cell-cycle activity. The specific complexes control access of factors such as E2F1, Tip60, and HDAC1/2/3 to the promoters of various cell-cycle-specific genes, with c-Myc emerging as a particularly critical target.
基于其调节增殖相关基因对转录因子的可及性的能力,哺乳动物的SWI/SNF染色质重塑复合体在肿瘤抑制中的作用越来越受到认可。然而,由于同一复合体似乎在基因表达中既起正向作用又起负向作用,了解该复合体的生物学作用变得很复杂。本文所述的研究揭示,在ARID蛋白家族一个主要亚基的两个独立编码、密切相关的变体之间做出的选择,决定了SWI/SNF复合体是否会与激活因子复合体或抑制因子复合体进一步结合。这种选择区分了对细胞周期活性有相反作用的组装体。特定的复合体控制着E2F1、Tip60和HDAC1/2/3等因子对各种细胞周期特异性基因启动子的可及性,其中c-Myc成为一个特别关键的靶点。