Positioning Heterochromatin at the Nuclear Periphery Suppresses Histone Turnover to Promote Epigenetic Inheritance

Cell. 2020 Jan 9;180(1):150-164.e15. doi: 10.1016/j.cell.2019.12.004. Epub 2019 Dec 26.

Abstract

In eukaryotes, heterochromatin is generally located at the nuclear periphery. This study investigates the biological significance of perinuclear positioning for heterochromatin maintenance and gene silencing. We identify the nuclear rim protein Amo1NUPL2 as a factor required for the propagation of heterochromatin at endogenous and ectopic sites in the fission yeast genome. Amo1 associates with the Rix1PELP1-containing RNA processing complex RIXC and with the histone chaperone complex FACT. RIXC, which binds to heterochromatin protein Swi6HP1 across silenced chromosomal domains and to surrounding boundary elements, connects heterochromatin with Amo1 at the nuclear periphery. In turn, the Amo1-enriched subdomain is critical for Swi6 association with FACT that precludes histone turnover to promote gene silencing and preserve epigenetic stability of heterochromatin. In addition to uncovering conserved factors required for perinuclear positioning of heterochromatin, these analyses elucidate a mechanism by which a peripheral subdomain enforces stable gene repression and maintains heterochromatin in a heritable manner.

Keywords: chromatin; epigenetic inheritance; gene regulation; heterochromatin; heterochromatin spreading; histone methylation; nuclear organization; nuclear periphery.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cell Nucleus / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Epigenesis, Genetic / genetics*
  • Epigenetic Repression / genetics
  • Gene Silencing
  • Heredity
  • Heterochromatin / genetics*
  • Heterochromatin / metabolism*
  • Histones / genetics
  • Histones / metabolism
  • Methylation
  • Nuclear Proteins / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Heterochromatin
  • Histones
  • Nuclear Proteins
  • Schizosaccharomyces pombe Proteins