Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA.
Nature. 2011 May 22;474(7352):516-20. doi: 10.1038/nature10002.
Nucleosomes are the basic packaging units of chromatin, modulating accessibility of regulatory proteins to DNA and thus influencing eukaryotic gene regulation. Elaborate chromatin remodelling mechanisms have evolved that govern nucleosome organization at promoters, regulatory elements, and other functional regions in the genome. Analyses of chromatin landscape have uncovered a variety of mechanisms, including DNA sequence preferences, that can influence nucleosome positions. To identify major determinants of nucleosome organization in the human genome, we used deep sequencing to map nucleosome positions in three primary human cell types and in vitro. A majority of the genome showed substantial flexibility of nucleosome positions, whereas a small fraction showed reproducibly positioned nucleosomes. Certain sites that position in vitro can anchor the formation of nucleosomal arrays that have cell type-specific spacing in vivo. Our results unveil an interplay of sequence-based nucleosome preferences and non-nucleosomal factors in determining nucleosome organization within mammalian cells.
核小体是染色质的基本包装单位，调节调节蛋白与 DNA 的可及性，从而影响真核基因调控。已经进化出精细的染色质重塑机制，可控制启动子、调控元件和基因组中其他功能区域的核小体组织。对染色质景观的分析揭示了多种可以影响核小体位置的机制，包括 DNA 序列偏好。为了确定人类基因组中核小体组织的主要决定因素，我们使用深度测序在三种主要的人类细胞类型和体外条件下绘制了核小体位置图谱。大多数基因组显示出核小体位置的显著灵活性，而一小部分显示出可重复定位的核小体。某些在体外定位的位点可以锚定核小体阵列的形成，这些核小体阵列在体内具有细胞类型特异性的间隔。我们的研究结果揭示了在哺乳动物细胞中，基于序列的核小体偏好与非核小体因子在决定核小体组织中的相互作用。
