Negative Regulators of an RNAi-Heterochromatin Positive Feedback Loop Safeguard Somatic Genome Integrity in Tetrahymena

Cell Rep. 2017 Mar 7;18(10):2494-2507. doi: 10.1016/j.celrep.2017.02.024.


RNAi-mediated positive feedback loops are pivotal for the maintenance of heterochromatin, but how they are downregulated at heterochromatin-euchromatin borders is not well understood. In the ciliated protozoan Tetrahymena, heterochromatin is formed exclusively on the sequences that are removed from the somatic genome by programmed DNA elimination, and an RNAi-mediated feedback loop is important for assembling heterochromatin on the eliminated sequences. In this study, we show that the heterochromatin protein 1 (HP1)-like protein Coi6p, its interaction partners Coi7p and Lia5p, and the histone demethylase Jmj1p are crucial for confining the production of small RNAs and the formation of heterochromatin to the eliminated sequences. The loss of Coi6p, Coi7p, or Jmj1p causes ectopic DNA elimination. The results provide direct evidence for the existence of a dedicated mechanism that counteracts a positive feedback loop between RNAi and heterochromatin at heterochromatin-euchromatin borders to maintain the integrity of the somatic genome.

Keywords: DNA elimination; Heterochromatin; RNAi; Tetrahymena; genome rearrangement; small RNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • DNA, Protozoan / metabolism
  • Feedback*
  • Genome, Protozoan*
  • Heterochromatin / metabolism*
  • Macronucleus / metabolism
  • Protein Binding
  • Protozoan Proteins / metabolism
  • RNA Interference*
  • Tetrahymena / genetics*


  • DNA, Protozoan
  • Heterochromatin
  • Protozoan Proteins