Topological polymorphism of nucleosome fibers and folding of chromatin

Biophys J. 2021 Feb 16;120(4):577-585. doi: 10.1016/j.bpj.2021.01.008. Epub 2021 Jan 16.

Abstract

We discuss recent observations of polymorphic chromatin packaging at the oligonucleosomal level and compare them with computer simulations. Our computations reveal two topologically different families of two-start 30-nm fiber conformations distinguished by the linker length L; fibers with L ≈ 10n and L ≈ 10n+5 basepairs have DNA linking numbers per nucleosome of ΔLk ≈ -1.5 and -1.0, respectively (where n is a natural number). Although fibers with ΔLk ≈ -1.5 were observed earlier, the topoisomer with ΔLk ≈ -1.0 is novel. These predictions were confirmed experimentally for circular nucleosome arrays with precisely positioned nucleosomes. We suggest that topological polymorphism of chromatin may play a role in transcription, with the {10n+5} fibers producing transcriptionally competent chromatin structures. This hypothesis is consistent with available data for yeast and, partially, for fly. We show that both fiber topoisomers (with ΔLk ≈ -1.5 and -1.0) have to be taken into account to interpret experimental data obtained using new techniques: genome-wide Micro-C, Hi-CO, and RICC-seq, as well as self-association of nucleosome arrays in vitro. The relative stability of these topoisomers is likely to depend on epigenetic histone modifications modulating the strength of internucleosome interactions. Potentially, our findings may reflect a general tendency of functionally distinct parts of the genome to retain topologically different higher-order structures.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Chromatin* / genetics
  • DNA
  • Models, Molecular
  • Molecular Conformation
  • Nucleosomes* / genetics

Substances

  • Chromatin
  • Nucleosomes
  • DNA