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.