Nucleosome-like structure from dendrimer-induced DNA compaction

Chun Jen Su*, Chun Yu Chen, Ming Champ Lin, Hsin Lung Chen, Hiroki Iwase, Satoshi Koizumi, Takeji Hashimoto

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

17 Scopus citations

Abstract

Genomic DNA in eukaryotes wraps around histone proteins to package into the limited space of cell nucleus. Since the precise structure of chromatin is not known in detail, attempts have been made to understand DNA-histone interaction and the associated self-organization behavior using synthetic model systems. Using small-angle X-ray and neutron scattering, here we show that the electrostatic attraction between DNA and polyamidoamine (PAMAM) dendrimer of generation nine (G9) led to the formation of beads-on-string structure, where DNA wrapped around the dendrimer tightly to yield the "chromatin-like fiber" composing of the interconnected "nucleosome-like particles". A "stiff chromatin-like fiber model" and a "wormlike chromatin-like fiber model" were introduced to obtain the theoretical scattering patterns closely resembling the experimentally observed ones, from which the pitch length (P) of the DNA superhelix wrapping around the dendrimer and the interparticle distance (d) of the nucleosome-like particles were deduced. Governed by the balance between the electrostatic interaction energy and DNA bending energy, P and d were found to decrease and increase with increasing charge density of dendrimer, respectively. The chromatin-like fibers formed at lower dendrimer charge densities exhibited certain conformational flexibility characterized by the orientation fluctuations of the nucleosome-like particles. The fiber however stiffened when the dendrimer charge density was increased to the extent that all the primary amine groups at the surface of the dendrimer were protonated. The present study revealed not only the accessibility of the beads-on-string structure by a potential model system for histone protein but also the effect of macrocation charge density on the DNA wrapping mode and the conformational feature associated with the chromatin-like fiber formed by the dendriplex.

Original languageEnglish
Pages (from-to)5208-5217
Number of pages10
JournalMacromolecules
Volume45
Issue number12
DOIs
StatePublished - 26 06 2012
Externally publishedYes

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