X-ray structure of a tetranucleosome and its implications for the chromatin fibre

X-ray structure of a tetranucleosome and its implications for the chromatin fibre
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DOI:
10.1038/nature03686
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发表时间:
2005-07-07
期刊:
影响因子:
64.8
通讯作者:
Richmond, TJ
Richmond, TJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Schalch, T;Duda, S;Richmond, TJ

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真核生物染色体中的DNA以核小体阵列的形式排列,核小体被压缩成染色质纤维。核小体的这种高级结构是DNA复制、重组、转录和修复的底物。虽然核小体核心的结构在近原子分辨率下是已知的(1),但即使是关于纤维中核小体组织的最基本信息也是有争议的。在这里,我们报告的晶体结构的一个nucleosome(一个紧凑的四核体)在9埃分辨率,解决了分子置换使用核小体核心结构。结构表明,连接DNA在两个核小体核心堆叠之间来回折叠,形成截短的双起始螺旋,并且不遵循与单起始螺线管螺旋相容的路径(2)。接头DNA的长度很可能是通过拉伸核小体核心中所含的DNA来缓冲的。我们已经建立了连续的纤维模型,连续堆叠四个核小体一个在另一个。所得到的模型几乎完全紧凑,并且最接近于先前描述的交联剂模型(3)。他们认为,核小体之间的界面沿着一个单一的螺旋开始是多态性的。
DNA in eukaryotic chromosomes is organized in arrays of nucleosomes compacted into chromatin fibres. This higher-order structure of nucleosomes is the substrate for DNA replication, recombination, transcription and repair. Although the structure of the nucleosome core is known at near-atomic resolution(1), even the most fundamental information about the organization of nucleosomes in the fibre is controversial. Here we report the crystal structure of an oligonucleosome (a compact tetranucleosome) at 9 angstrom resolution, solved by molecular replacement using the nucleosome core structure. The structure shows that linker DNA zigzags back and forth between two stacks of nucleosome cores, which forma truncated two-start helix, and does not follow a path compatible with a one-start solenoidal helix(2). The length of linker DNA is most probably buffered by stretching of the DNA contained in the nucleosome cores. We have built continuous fibre models by successively stacking tetranucleosomes one on another. The resulting models are nearly fully compacted and most closely resemble the previously described crossed-linker model(3). They suggest that the interfaces between nucleosomes along a single helix start are polymorphic.