Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10165-70. doi: 10.1073/pnas.1302209110. Epub 2013 May 30.
Precise nucleosome-positioning patterns at promoters are thought to be crucial for faithful transcriptional regulation. However, the mechanisms by which these patterns are established, are dynamically maintained, and subsequently contribute to transcriptional control are poorly understood. The switch/sucrose non-fermentable chromatin remodeling complex, also known as the Brg1 associated factors complex, is a master developmental regulator and tumor suppressor capable of mobilizing nucleosomes in biochemical assays. However, its role in establishing the nucleosome landscape in vivo is unclear. Here we have inactivated Snf5 and Brg1, core subunits of the mammalian Swi/Snf complex, to evaluate their effects on chromatin structure and transcription levels genomewide. We find that inactivation of either subunit leads to disruptions of specific nucleosome patterning combined with a loss of overall nucleosome occupancy at a large number of promoters, regardless of their association with CpG islands. These rearrangements are accompanied by gene expression changes that promote cell proliferation. Collectively, these findings define a direct relationship between chromatin-remodeling complexes, chromatin structure, and transcriptional regulation.
精确的启动子核小体定位模式被认为对忠实的转录调控至关重要。然而，这些模式是如何建立的、如何动态维持的，以及随后如何促进转录控制，这些机制还知之甚少。开关/蔗糖非发酵性染色质重塑复合物，也称为 Brg1 相关因子复合物，是一种主要的发育调节剂和肿瘤抑制剂，能够在生化分析中动员核小体。然而，其在体内建立核小体景观的作用尚不清楚。在这里，我们失活了哺乳动物 Swi/Snf 复合物的核心亚基 Snf5 和 Brg1，以评估它们对染色质结构和全基因组转录水平的影响。我们发现，失活任一亚基都会导致特定核小体模式的破坏，同时大量启动子的核小体占有率整体丧失，而与 CpG 岛无关。这些重排伴随着促进细胞增殖的基因表达变化。总的来说，这些发现定义了染色质重塑复合物、染色质结构和转录调控之间的直接关系。
