DNA deletion as a mechanism for developmentally programmed centromere loss.
A hallmark of active centromeres is the presence of the histone H3 variant CenH3 in the centromeric chromatin, which ensures faithful genome distribution at each cell division. A functional centromere can be inactivated, but the molecular mechanisms underlying the process of centromere inactivation remain largely unknown. Here, we describe the loss of CenH3 protein as part of a developmental program leading to the formation of the somatic nucleus in the eukaryote Paramecium. We identify two proteins whose depletion prevents developmental loss of CenH3: the domesticated transposase Pgm involved in the formation of DNA double strand cleavages and the Polycomb-like lysine methyltransferase Ezl1 necessary for trimethylation of histone H3 on lysine 9 and lysine 27. Taken together, our data support a model in which developmentally programmed centromere loss is caused by the elimination of DNA sequences associated with CenH3.
Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, Paris, F-75205 France.
Maoussi
M
Lhuillier-Akakpo
Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, Paris, F-75205 France.
Frédéric
F
Guérin
Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, Paris, F-75205 France.
Andrea
A
Frapporti
Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, Paris, F-75205 France sandra.duharcourt@ijm.fr.
Sandra
S
Duharcourt
D001324:Autoantigens / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics; D002503:Centromere / Q000235:genetics*; D000076247:Centromere Protein A; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D006657:Histones / Q000235:genetics; D010247:Paramecium / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*; D019895:Transposases / Q000235:genetics
D001324:Autoantigens; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D004247:DNA; D019895:Transposases