Regulatory motifs on ISWI chromatin remodelers: molecular mechanisms and kinetic proofreading

J Phys Condens Matter. 2015 Feb 18;27(6):064108. doi: 10.1088/0953-8984/27/6/064108. Epub 2015 Jan 7.

Abstract

Recently, kinetic proofreading scenarios have been proposed for the regulation of chromatin remodeling, first on purely theoretical grounds (Blossey and Schiessel 2008 HFSP J. 2 167-70) and deduced from experiments on the ISWI/ACF system (Narlikar 2010 Curr. Opin. Chem. Biol. 14 660). In the kinetic proofreading scenario of chromatin remodeling, the combination of the recognition of a histone tail state and ATP-hydrolysis in the remodeler motor act together to select (i.e. proofread) a nucleosomal substrate. ISWI remodelers have recently been shown to have an additional level of regulation as they contain auto-inhibitory motifs which need to be inactivated through an interaction with the nucleosome. In this paper we show that the auto-regulatory effect enhances substrate recognition in kinetic proofreading. We further report some suggestive additional insights into the molecular mechanism underlying ISWI-autoregulation.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Motifs
  • Chromatin Assembly and Disassembly*
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism
  • Homeostasis*
  • Kinetics
  • Models, Molecular
  • Nucleic Acid Conformation

Substances

  • Histones
  • Adenosine Triphosphate