Kharchenko Peter V, Woo Caroline J, Tolstorukov Michael Y, Kingston Robert E, Park Peter J
Harvard Partners Center for Genetics and Genomics, Boston, Massachusetts 02115, USA.
Genome Res. 2008 Oct;18(10):1554-61. doi: 10.1101/gr.075952.107. Epub 2008 Aug 22.
The distribution of nucleosomes along the genome is a significant aspect of chromatin structure and is thought to influence gene regulation through modulation of DNA accessibility. However, properties of nucleosome organization remain poorly understood, particularly in mammalian genomes. Toward this goal we used tiled microarrays to identify stable nucleosome positions along the HOX gene clusters in human cell lines. We show that nucleosome positions exhibit sequence properties and long-range organization that are different from those characterized in other organisms. Despite overall variability of internucleosome distances, specific loci contain regular nucleosomal arrays with 195-bp periodicity. Moreover, such arrays tend to occur preferentially toward the 3' ends of genes. Through comparison of different cell lines, we find that active transcription is correlated with increased positioning of nucleosomes, suggesting an unexpected role for transcription in the establishment of well-positioned nucleosomes.
核小体沿基因组的分布是染色质结构的一个重要方面,并且被认为通过调节DNA可及性来影响基因调控。然而,核小体组织的特性仍知之甚少,尤其是在哺乳动物基因组中。为了实现这一目标,我们使用平铺式微阵列来确定人类细胞系中HOX基因簇沿线的稳定核小体位置。我们发现核小体位置呈现出与其他生物体中所描述的不同的序列特性和长程组织。尽管核小体间距离总体上存在变异性,但特定基因座包含具有195碱基对周期性的规则核小体阵列。此外,这种阵列倾向于优先出现在基因的3'端。通过比较不同的细胞系,我们发现活跃转录与核小体定位增加相关,这表明转录在定位良好的核小体的建立中具有意想不到的作用。