Dynamics of nucleosome invasion by DNA binding proteins

Hannah S. Tims, Kaushik Gurunathan, Marcia Levitus, Jonathan Widom

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

Nucleosomes sterically occlude their wrapped DNA from interacting with many large protein complexes. How proteins gain access to nucleosomal DNA target sites in vivo is not known. Outer stretches of nucleosomal DNA spontaneously unwrap and rewrap with high frequency, providing rapid and efficient access to regulatory DNA target sites located there; however, rates for access to the nucleosome interior have not been measured. Here we show that for a selected high-affinity nucleosome positioning sequence, the spontaneous DNA unwrapping rate decreases dramatically with distance inside the nucleosome. The rewrapping rate also decreases, but only slightly. Our results explain the previously known strong position dependence on the equilibrium accessibility of nucleosomal DNA, which is characteristic of both selected and natural sequences. Our results point to slow nucleosome conformational fluctuations as a potential source of cell-cell variability in gene activation dynamics, and they reveal the dominant kinetic path by which multiple DNA binding proteins cooperatively invade a nucleosome.

Original languageEnglish (US)
Pages (from-to)430-448
Number of pages19
JournalJournal of molecular biology
Volume411
Issue number2
DOIs
StatePublished - Aug 12 2011

Keywords

  • chromatin
  • fluorescence correlation spectroscopy
  • fluorescence resonance energy transfer
  • gene regulation
  • transcription factor

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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