From crystal and NMR structures, footprints and cryo-electron-micrographs to large and soft structures: Nanoscale modeling of the nucleosomal stem

Sam Meyer, Nils B. Becker, Sajad Hussain Syed, Damien Goutte-Gattat, Manu Shubhdarshan Shukla, Jeffrey J. Hayes, Dimitar Angelov, Jan Bednar, Stefan Dimitrov, Ralf Everaers

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Abstract

The interaction of histone H1 with linker DNA results in the formation of the nucleosomal stem structure, with considerable influence on chromatin organization. In a recent paper [Syed,S.H., Goutte-Gattat,D., Becker,N., Meyer,S., Shukla,M.S., Hayes,J.J., Everaers,R., Angelov,D., Bednar,J. and Dimitrov,S. (2010) Single-base resolution mapping of H1-nucleosome interactions and 3D organization of the nucleosome. Proc. Natl Acad. Sci. USA, 107, 9620-9625], we published results of biochemical footprinting and cryo-electron-micrographs of reconstituted mono-, di-and tri-nucleosomes, for H1 variants with different lengths of the cationic C-terminus. Here, we present a detailed account of the analysis of the experimental data and we include thermal fluctuations into our nano-scale model of the stem structure. By combining (i) crystal and NMR structures of the nucleosome core particle and H1, (ii) the known nano-scale structure and elasticity of DNA, (iii) footprinting information on the location of protected sites on the DNA backbone and (iv) cryo-electron micrographs of reconstituted tri-nucleosomes, we arrive at a description of a polymorphic, hierarchically organized stem with a typical length of 20±2 base pairs. A comparison to linker conformations inferred for poly-601 fibers with different linker lengths suggests, that intra-stem interactions stabilize and facilitate the formation of dense chromatin fibers.

Original languageEnglish
Pages (from-to)9139-9154
Number of pages16
JournalNucleic Acids Research
Volume39
Issue number21
DOIs
Publication statusPublished - Nov 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Meyer, S., Becker, N. B., Syed, S. H., Goutte-Gattat, D., Shukla, M. S., Hayes, J. J., Angelov, D., Bednar, J., Dimitrov, S., & Everaers, R. (2011). From crystal and NMR structures, footprints and cryo-electron-micrographs to large and soft structures: Nanoscale modeling of the nucleosomal stem. Nucleic Acids Research, 39(21), 9139-9154. https://doi.org/10.1093/nar/gkr573