title: Negative Regulators of an RNAi-Heterochromatin Positive Feedback Loop Safeguard Somatic Genome Integrity in Tetrahymena.
abstract: 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.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Suhren
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria; Institute of Human Genetics, CNRS-University of Montpellier UMR9002, 34396 Montpellier, France.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Noto
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Pathology Department, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Pathology Department, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria; Institute of Human Genetics, CNRS-University of Montpellier UMR9002, 34396 Montpellier, France. Electronic address: kazufumi.mochizuki@igh.cnrs.fr.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Mochizuki
mesh_terms: D001483:Base Sequence; D016054:DNA, Protozoan / Q000378:metabolism; D005246:Feedback; D018503:Genome, Protozoan; D006570:Heterochromatin / Q000378:metabolism*; D048648:Macronucleus / Q000378:metabolism; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism; D034622:RNA Interference; D013768:Tetrahymena / Q000235:genetics*
chemical_list: D016054:DNA, Protozoan; D006570:Heterochromatin; D015800:Protozoan Proteins
keywords: DNA elimination; Heterochromatin; RNAi; Tetrahymena; genome rearrangement; small RNAs