Zhang Yong, Shin Hyunjin, Song Jun S, Lei Ying, Liu X Shirley
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, 44 Binney St, Boston, MA 02115, USA.
BMC Genomics. 2008 Nov 13;9:537. doi: 10.1186/1471-2164-9-537.
In vivo positioning and covalent modifications of nucleosomes play an important role in epigenetic regulation, but genome-wide studies of positioned nucleosomes and their modifications in human still remain limited.
This paper describes a novel computational framework to efficiently identify positioned nucleosomes and their histone modification profiles from nucleosome-resolution histone modification ChIP-Seq data. We applied the algorithm to histone methylation ChIP-Seq data in human CD4+ T cells and identified over 438,000 positioned nucleosomes, which appear predominantly at functionally important regions such as genes, promoters, DNase I hypersensitive regions, and transcription factor binding sites. Our analysis shows the identified nucleosomes play a key role in epigenetic gene regulation within those functionally important regions via their positioning and histone modifications.
Our method provides an effective framework for studying nucleosome positioning and epigenetic marks in mammalian genomes. The algorithm is open source and available at http://liulab.dfci.harvard.edu/NPS/.
核小体的体内定位和共价修饰在表观遗传调控中起着重要作用,但在人类中对定位核小体及其修饰进行全基因组研究仍然有限。
本文描述了一种新颖的计算框架,可从核小体分辨率的组蛋白修饰ChIP-Seq数据中高效识别定位核小体及其组蛋白修饰谱。我们将该算法应用于人类CD4+ T细胞中的组蛋白甲基化ChIP-Seq数据,识别出超过438,000个定位核小体,这些核小体主要出现在基因、启动子、DNase I超敏区域和转录因子结合位点等功能重要区域。我们的分析表明,所识别的核小体通过其定位和组蛋白修饰在这些功能重要区域内的表观遗传基因调控中起关键作用。
我们的方法为研究哺乳动物基因组中的核小体定位和表观遗传标记提供了一个有效的框架。该算法是开源的,可在http://liulab.dfci.harvard.edu/NPS/获取。