Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome

Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome
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DOI:
10.1038/nature05632
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发表时间:
2007-03-29
期刊:
影响因子:
64.8
通讯作者:
Pugh, B. Franklin
Pugh, B. Franklin
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Albert, Istvan;Mavrich, Travis N.;Pugh, B. Franklin

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核小体是真核生物染色体的基本组成部分。获取染色体中编码的遗传信息取决于核小体沿着DNA的位置。仅相隔几个核苷酸的替代位置可以对基因表达产生深远的影响(1)。然而,染色体和基因调控元件所处的核小体环境在基因组尺度上仍然定义不清。在这里,我们对322,000个含有组蛋白变体H2A.Z的酿酒酵母核小体的DNA进行测序,以提供功能重要区域的H2A.Z核小体的综合图谱。与中位数4碱基对分辨率,我们确定新的和建立的核小体定位的签名。一个单一的主要旋转设置和多个平移设置是显而易见的。染色体元件,从端粒到着丝粒和转录单位,被发现具有特征性的核小体结构,这可能对它们的功能很重要。启动子调控元件,包括转录因子结合位点和转录起始位点,显示与核小体的拓扑关系,使得转录因子结合位点倾向于旋转地暴露在核小体表面上靠近其边界。转录起始位点倾向于位于核小体边界内的一个螺旋圈。这些发现揭示了染色质结构与其调控的潜在DNA序列之间的密切关系。
The nucleosome is the fundamental building block of eukaryotic chromosomes. Access to genetic information encoded in chromosomes is dependent on the position of nucleosomes along the DNA. Alternative locations just a few nucleotides apart can have profound effects on gene expression(1). Yet the nucleosomal context in which chromosomal and gene regulatory elements reside remains ill-defined on a genomic scale. Here we sequence the DNA of 322,000 individual Saccharomyces cerevisiae nucleosomes, containing the histone variant H2A.Z, to provide a comprehensive map of H2A.Z nucleosomes in functionally important regions. With a median 4-base-pair resolution, we identify new and established signatures of nucleosome positioning. A single predominant rotational setting and multiple translational settings are evident. Chromosomal elements, ranging from telomeres to centromeres and transcriptional units, are found to possess characteristic nucleosomal architecture that may be important for their function. Promoter regulatory elements, including transcription factor binding sites and transcriptional start sites, show topological relationships with nucleosomes, such that transcription factor binding sites tend to be rotationally exposed on the nucleosome surface near its border. Transcriptional start sites tended to reside about one helical turn inside the nucleosome border. These findings reveal an intimate relationship between chromatin architecture and the underlying DNA sequence it regulates.