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 resolution1, 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 Å 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 form a truncated two-start helix, and does not follow a path compatible with a one-start solenoidal helix2. 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 model3. They suggest that the interfaces between nucleosomes along a single helix start are polymorphic.
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We thank C. Schulze-Briese, T. Tomizaki and A. Wagner for assistance in data collection, and J. Widom for providing us with the 601 sequence.
Coordinates have been deposited in the Protein Data Bank with identifier 1zbb. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
Explanation of the packing disorder found in the tetranucleosome crystals. (PDF 96 kb)
Small angle X-ray scattering (SAXS) distributions for chicken erythrocyte chromatin and three chromatin fibre models. (PDF 54 kb)
Description of the sequence and preparation of the DNA contained in the tetranucleosome. (PDF 11 kb)
Statistics of the X-ray crystallographic structure determination. (PDF 50 kb)
Tetranucleosome with axis system displayed (video version of Fig. 1c). (WMV 7692 kb)
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Schalch, T., Duda, S., Sargent, D. et al. X-ray structure of a tetranucleosome and its implications for the chromatin fibre. Nature 436, 138–141 (2005) doi:10.1038/nature03686
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