A tale of tails: how histone tails mediate chromatin compaction in different salt and linker histone environments.

Published

Journal Article

To elucidate the role of the histone tails in chromatin compaction and in higher-order folding of chromatin under physiological conditions, we extend a mesoscale model of chromatin (Arya, Zhang, and Schlick. Biophys. J. 2006, 91, 133; Arya and Schlick. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 16236) to account for divalent cations (Mg(2+)) and linker histones. Configurations of 24-nucleosome oligonucleosomes in different salt environments and in the presence and absence of linker histones are sampled by a mixture of local and global Monte Carlo methods. Analyses of the resulting ensembles reveal a dynamic synergism between the histone tails, linker histones, and ions in forming compact higher-order structures of chromatin. In the presence of monovalent salt alone, oligonucleosomes remain relatively unfolded, and the histone tails do not mediate many internucleosomal interactions. Upon the addition of linker histones and divalent cations, the oligonucleosomes undergo a significant compaction triggered by a dramatic increase in the internucleosomal interactions mediated by the histone tails, formation of a rigid linker DNA "stem" around the linker histones' C-terminal domains, and reduction in the electrostatic repulsion between linker DNAs via sharp bending in some linker DNAs caused by the divalent cations. Among all histone tails, the H4 tails mediate the most internucleosomal interactions, consistent with experimental observations, followed by the H3, H2A, and H2B tails in decreasing order. Apart from mediating internucleosomal interactions, the H3 tails also contribute to chromatin compaction by attaching to the entering and exiting linker DNA to screen electrotatic repulsion among the linker DNAs. This tendency of the H3 tails to attach to linker DNA, however, decreases significantly upon the addition of linker histones due to competition effects. The H2A and H2B tails do not mediate significant internucleosomal interactions but are important for mediating fiber/fiber intractions, especially in relatively unfolded chromatin in monovalent salt environments.

Full Text

Duke Authors

Cited Authors

  • Arya, G; Schlick, T

Published Date

  • April 2009

Published In

Volume / Issue

  • 113 / 16

Start / End Page

  • 4045 - 4059

PubMed ID

  • 19298048

Pubmed Central ID

  • 19298048

Electronic International Standard Serial Number (EISSN)

  • 1520-5215

International Standard Serial Number (ISSN)

  • 1089-5639

Digital Object Identifier (DOI)

  • 10.1021/jp810375d

Language

  • eng