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

Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Jan H. Suhren, Tomoko Noto, Kensuke Kataoka, Shan Gao, Yifan Liu, Kazufumi Mochizuki
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.

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Teaser

Regulation of a small RNA-mediated positive feedback loop is pivotal for confining heterochromatin to proper locations. Suhren et al. show the existence of a dedicated mechanism that counteracts a small RNA-heterochromatin positive feedback loop at heterochromatin-euchromatin borders to maintain the integrity of the somatic genome in Tetrahymena.


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