Abstract
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.
Highlights
The centromere is the specialized chromosomal region that defines the assembly sites for the kinetochore and is essential for faithful genome distribution at each cell division
In order to identify the centromeric histone CenH3 of P. tetraurelia, we first searched for histone H3 homologues in the MAC genome assembly [25,26]
We have identified the Paramecium tetraurelia centromeric protein CenH3a
Summary
The centromere is the specialized chromosomal region that defines the assembly sites for the kinetochore and is essential for faithful genome distribution at each cell division. Functional centromeres are marked by the presence of the histone H3 variant CenH3 that replaces canonical H3 in centromeric nucleosomes. Chromosomes contain a single region where centromere DNA sequences assemble kinetochores. Genome rearrangements can lead to the accidental emergence of an additional centromere on the same chromosome. Such dicentric chromosomes are generally unstable during mitosis [2,3], but can give rise to functionally monocentric chromosomes that segregate normally during cell division, when one centromere is inactivated [4]. The molecular mechanisms underlying the process of centromere inactivation are still poorly understood, even though several studies suggested two possible pathways: (i) deletion of centromere DNA sequences and (ii) epigenetic inactivation when centromeric DNA is retained but CenH3 is absent [7,8,9,10,11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
