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Centromere-specifying nucleosomes persist in aging mouse oocytes in the absence of nascent assembly

View ORCID ProfileArunika Das, Katelyn G. Boese, Kikue Tachibana, Sung Hee Baek, View ORCID ProfileMichael A. Lampson, Ben E. Black
doi: https://doi.org/10.1101/2023.05.18.541332
Arunika Das
1Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
2Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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  • ORCID record for Arunika Das
Katelyn G. Boese
1Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
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Kikue Tachibana
3Department of Totipotency, Max Planck Institute of Biochemistry, Martinsried 82152, Germany
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Sung Hee Baek
4Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826
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Michael A. Lampson
1Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
6Penn Center for Genome Integrity, University of Pennsylvania, Philadelphia, PA 19104, USA
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  • For correspondence: blackbe@pennmedicine.upenn.edu lampson@sas.upenn.edu
Ben E. Black
2Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5Epigenetics Institute; University of Pennsylvania, Philadelphia PA 19104, USA
6Penn Center for Genome Integrity, University of Pennsylvania, Philadelphia, PA 19104, USA
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  • For correspondence: blackbe@pennmedicine.upenn.edu lampson@sas.upenn.edu
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Abstract

SUMMARY Centromeres direct genetic inheritance but are not themselves genetically encoded. Instead, centromeres are defined epigenetically by the presence of a histone H3 variant, CENP-A1. In cultured somatic cells, an established paradigm of cell cycle-coupled propagation maintains centromere identity: CENP-A is partitioned between sisters during replication and replenished by new assembly, which is restricted to G1. The mammalian female germline challenges this model because of the cell cycle arrest between pre-meiotic S-phase and the subsequent G1, which can last for the entire reproductive lifespan (months to decades). New CENP-A chromatin assembly maintains centromeres during prophase I in worm and starfish oocyte2,3, suggesting that a similar process may be required for centromere inheritance in mammals. However, we show that centromere chromatin is maintained long-term independent of new assembly during the extended prophase I arrest in mouse oocytes. Conditional knockout of Mis18α, an essential component of the assembly machinery, in the female germline at the time of birth has almost no impact on centromeric CENP-A nucleosome abundance nor any detectable detriment to fertility.

Competing Interest Statement

The authors have declared no competing interest.

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Posted May 18, 2023.
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Centromere-specifying nucleosomes persist in aging mouse oocytes in the absence of nascent assembly
Arunika Das, Katelyn G. Boese, Kikue Tachibana, Sung Hee Baek, Michael A. Lampson, Ben E. Black
bioRxiv 2023.05.18.541332; doi: https://doi.org/10.1101/2023.05.18.541332
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Centromere-specifying nucleosomes persist in aging mouse oocytes in the absence of nascent assembly
Arunika Das, Katelyn G. Boese, Kikue Tachibana, Sung Hee Baek, Michael A. Lampson, Ben E. Black
bioRxiv 2023.05.18.541332; doi: https://doi.org/10.1101/2023.05.18.541332

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