Ten principles of heterochromatin formation and function

Robin C. Allshire, Hiten D. Madhani

Research output: Contribution to journalReview articlepeer-review

Abstract

Heterochromatin is a critical architectural unit of eukaryotic chromosomes. It endows particular genomic domains with specific functional properties. Critical is the role of heterochromatin in genomic stability, which is mediated by its ability to restrain mobile elements, isolate repair events in repetitive regions, and to contribute to the formation of structures that ensure accurate chromosome segregation. This distinctive chromatin also contributes to developmental regulation by restricting the accessible compartment of the genome in specific lineages. The establishment and maintenance mechanisms that mediate heterochromatin assembly are separable and involve the ability of sequence-specific factors, modified chromatin and nascent transcript-bound proteins to recruit chromatin-modifying enzymes. Heterochromatin can spread along the chromatin fiber from nucleation sites and also mediates its own epigenetic inheritance through cell division, yet these propensities are normally strongly repressed. Due to its central importance in chromosome biology, heterochromatin plays key roles in the pathogenesis of various human diseases. In this article, we derive these broadly conserved principles of heterochromatin formation and function using selected examples from studies of a range of eukaryotic model organisms from yeast to man, with an emphasis on insights obtained from unicellular systems.
Original languageEnglish
Number of pages16
JournalNature reviews Molecular cell biology
Early online date13 Dec 2017
DOIs
Publication statusE-pub ahead of print - 13 Dec 2017

Keywords

  • Chromatin remodelling
  • DNA methylation
  • Gene silencing
  • Methylation

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