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The SWI/SNF tumor suppressor complex

机译：SWI / SNF抑癌复合物

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Nucleosomes, octamers of histones wrapped in 147 bp of DNA, are the basic unit of chromatin. In eukaryotic cells, the placement of nucleosomes along the genome is highly organized, and modulation of this ordered arrangement contributes to regulation of gene expression. The SWI/SNF complex utilizes the energy of ATP hydrolysis to mobilize nucleosomes and remodel chromatin structure. Recently, the complex has also been implicated in oncogenesis as genes encoding multiple SWI/SNF subunits have been found mutated at high frequency across a wide spectrum of cancers. Given that epigenetic aberrations are now characterized as a hallmark of human cancer, hypotheses have been put forth that the SWI/SNF complex inhibits tumor formation by regulating key chromatin functions. To understand how the SWI/SNF complex contributes to nucleosome organization in vivo we performed a genome-wide study in mammalian cells. We found that inactivation of SWI/SNF subunits leads to disruptions of specific nucleosome patterning and a loss of nucleosome occupancy at a large number of promoters. These findings define a direct relationship between the SWI/SNF complex, chromatin structure, and transcriptional regulation. In this extra view, we discuss our findings, their relevance to gene regulation, and possible links to the tumor suppression activities of the SWI/SNF complex.
机译：核小体是包裹在147 bp DNA中的组蛋白的八聚体，是染色质的基本单位。在真核细胞中，核小体沿基因组的排列是高度有组织的，这种有序排列的调节有助于基因表达的调节。 SWI / SNF复合物利用ATP水解的能量来动员核小体并重塑染色质结构。最近，该复合物也与肿瘤发生有关，因为已发现编码多种SWI / SNF亚基的基因在多种癌症中均以高频率突变。鉴于现在将表观遗传畸变表征为人类癌症的标志，提出了这样的假设：SWI / SNF复合体通过调节关键的染色质功能来抑制肿瘤形成。为了了解SWI / SNF复合物如何在体内促进核小体的组织形成，我们在哺乳动物细胞中进行了全基因组研究。我们发现SWI / SNF亚基的失活导致特定的核小体模式的破坏和大量启动子的核小体占有率的损失。这些发现确定了SWI / SNF复合物，染色质结构和转录调控之间的直接关系。在这个额外的观点中，我们讨论了我们的发现，它们与基因调控的相关性以及与SWI / SNF复合体的肿瘤抑制活性的可能联系。

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