Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure

PLoS Comput Biol. 2017 Jan 30;13(1):e1005365. doi: 10.1371/journal.pcbi.1005365. eCollection 2017 Jan.

Abstract

Why most of the in vivo experiments do not find the 30-nm chromatin fiber, well studied in vitro, is a puzzle. Two basic physical inputs that are crucial for understanding the structure of the 30-nm fiber are the stiffness of the linker DNA and the relative orientations of the DNA entering/exiting nucleosomes. Based on these inputs we simulate chromatin structure and show that the presence of non-histone proteins, which bind and locally bend linker DNA, destroys any regular higher order structures (e.g., zig-zag). Accounting for the bending geometry of proteins like nhp6 and HMG-B, our theory predicts phase-diagram for the chromatin structure as a function of DNA-bending non-histone protein density and mean linker DNA length. For a wide range of linker lengths, we show that as we vary one parameter, that is, the fraction of bent linker region due to non-histone proteins, the steady-state structure will show a transition from zig-zag to an irregular structure-a structure that is reminiscent of what is observed in experiments recently. Our theory can explain the recent in vivo observation of irregular chromatin having co-existence of finite fraction of the next-neighbor (i + 2) and neighbor (i + 1) nucleosome interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chromatin / chemistry*
  • Chromatin / ultrastructure*
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / ultrastructure*
  • Computer Simulation
  • DNA / chemistry*
  • DNA / ultrastructure*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / ultrastructure
  • Elastic Modulus
  • Models, Chemical
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • DNA

Grants and funding

We acknowledge financial support from Council of Scientific and Industrial Research India (Grant no.37(1582)/13/EMR-II to RP and 03(1326)/14/EMR-II to DD) http://www.csir.res.in/, and Innovative Young Biotechnologist Award, Department of Biotechnology, Ministry of Science and Technology India (to RP) http://www.dbtindia.nic.in/funding-mechanism/awards/#4. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.