Oligonucleotide sequence motifs as nucleosome positioning signals.

Oligonucleotide sequence motifs as nucleosome positioning signals.
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DOI:
10.1371/journal.pone.0010933
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发表时间:
2010-06-03
期刊:
影响因子:
3.7
通讯作者:
Anderson JN
Anderson JN
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Collings CK;Fernandez AG;Pitschka CG;Hawkins TB;Anderson JN

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为了更好地了解定位核小体的序列模式,我们首先进行了分析的周期性的256个四核苷酸在酵母全基因组的核小体DNA序列,在体外重建制备的文库。该方法需要鉴定和分析由8个共有序列定义的24个独特的四核苷酸。这些共有序列被证明是负责大部分,如果不是所有的四核苷酸和二核苷酸周期性显示的整个文库,表明,表征酵母基因组的二核苷酸的周期性,在现实中,主要是由于8个共有序列。一种新的实验和生物信息学方法的组合,然后被用来表明,这些四核苷酸是重要的,在特定的网站沿着DNA在体外的核小体的优先形成。然后将这些结果与来自酵母和C.为了评估DNA序列在控制细胞中核小体驻留中的贡献,这些比较揭示了惊人的相似性,在四核苷酸发生的配置文件,可能参与核小体定位在体外和体内库,这表明DNA序列是一个重要的因素,在控制体内的核小体放置。然而,与体内文库相比,体外四核苷酸周期性的强度高3-4倍,这意味着DNA序列在体内决定核小体位置中起的作用较小。本研究的结果具有重要意义的模型序列依赖的定位,因为它们表明,一个定义的子集的四核苷酸参与优选的核小体占用,这些四核苷酸是主要来源的二核苷酸周期性的特征定位的核小体。
To gain a better understanding of the sequence patterns that characterize positioned nucleosomes, we first performed an analysis of the periodicities of the 256 tetranucleotides in a yeast genome-wide library of nucleosomal DNA sequences that was prepared by in vitro reconstitution. The approach entailed the identification and analysis of 24 unique tetranucleotides that were defined by 8 consensus sequences. These consensus sequences were shown to be responsible for most if not all of the tetranucleotide and dinucleotide periodicities displayed by the entire library, demonstrating that the periodicities of dinucleotides that characterize the yeast genome are, in actuality, due primarily to the 8 consensus sequences. A novel combination of experimental and bioinformatic approaches was then used to show that these tetranucleotides are important for preferred formation of nucleosomes at specific sites along DNA in vitro. These results were then compared to tetranucleotide patterns in genome-wide in vivo libraries from yeast and C. elegans in order to assess the contributions of DNA sequence in the control of nucleosome residency in the cell. These comparisons revealed striking similarities in the tetranucleotide occurrence profiles that are likely to be involved in nucleosome positioning in both in vitro and in vivo libraries, suggesting that DNA sequence is an important factor in the control of nucleosome placement in vivo. However, the strengths of the tetranucleotide periodicities were 3–4 fold higher in the in vitro as compared to the in vivo libraries, which implies that DNA sequence plays less of a role in dictating nucleosome positions in vivo. The results of this study have important implications for models of sequence-dependent positioning since they suggest that a defined subset of tetranucleotides is involved in preferred nucleosome occupancy and that these tetranucleotides are the major source of the dinucleotide periodicities that are characteristic of positioned nucleosomes.
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