Linker histones and chromatin remodelling complexes maintain genome stability and control cellular ageing

Mech Ageing Dev. 2019 Jan:177:55-65. doi: 10.1016/j.mad.2018.07.002. Epub 2018 Jul 17.

Abstract

Linker histones are major players in chromatin organization and per se are essential players in genome homeostasis. As the fifth class of histone proteins the linker histones not only interact with DNA and core histones but also with other chromatin proteins. These interactions prove to be essential for the higher levels of chromatin organization like chromatin loops, transcription factories and chromosome territories. Our recent results have proved that Saccharomyces cerevisiae linker histone - Hho1p, physically interacts with the actin-related protein 4 (Arp4) and that the abrogation of this interaction through the deletion of the gene for the linker histone in arp4 mutant cells leads to global changes in chromatin compaction. Here, we show that the healthy interaction between the yeast linker histone and Arp4p is critical for maintaining genome stability and for controlling cellular sensitivity to different types of stress. The abolished interaction between the linker histone and Arp4p leads the mutant yeast cells to premature ageing phenotypes. Cells die young and are more sensitive to stress. These results unambiguously prove the role of linker histones and chromatin remodelling in ageing by their cooperation in pertaining higher-order chromatin compaction and thus maintaining genome stability.

Keywords: Actin-related protein 4; Chromatin remodelling; Chronological ageing; Linker histones; Saccharomyces cerevisiae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Chromatin Assembly and Disassembly / physiology*
  • Gene Expression Regulation, Fungal / physiology*
  • Genomic Instability / physiology*
  • Histones / genetics
  • Histones / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Actins
  • Arp4 protein, S cerevisiae
  • HHO1 protein, S cerevisiae
  • Histones
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins