Dynamic regulation of nucleosome positioning in the human genome
Dynamic regulation of nucleosome positioning in the human genome
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DOI：
10.1016/j.cell.2008.02.022
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发表时间：
2008-03-07
期刊：
影响因子：
64.5
通讯作者：
Zhao, Keji
中科院分区：
文献类型：
--
作者：
Schones, Dustin E.;Cui, Kairong;Zhao, Keji
核小体相对于DNA的定位在转录调控中起着重要作用。然而，核小体图谱只对人类有限的基因组区域进行了绘制。我们已经通过使用Solexa高通量测序技术对核小体末端进行直接测序，生成了静息和激活的人类CD4(+)T细胞中核小体位置的全基因组图谱。我们发现，核小体相对于转录起始点的阶段与RNA聚合酶II(POL II)的结合直接相关。此外，起始点下游的第一个核小体在活跃基因和沉默基因中显示出不同的定位。TCR信号在启动子和增强子中诱导广泛的核小体重组，从而允许转录激活或抑制。我们的结果表明，含有H2A.Z的和修饰的核小体优先从-1核小体位置丢失。我们的数据提供了对人类基因组中核小体格局及其动态调控的全面看法。
The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4(+) T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. We find that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore, the first nucleosome downstream of a start site exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome.