Set mediates chromosome alignment and Cohesin cleavage independently of direct PP2A-B56-binding in oocyte meiosis
Abstract
Set promotes cohesion removal in mitosis by evicting phosphorylated Histone H1 and counteracting Sgo1. In addition, Set promotes chromosome alignment by counteracting Aurora B activation. The underlying molecular mechanisms through which Set performs these activities remain insufficiently characterized, but roles of Set as a Histone chaperone and PP2A inhibitor have been proposed. Building on our previous observations that Set promotes pericentromeric Cohesin removal in oocyte meiosis II, we generated an oocyte-specific conditional knock-out of Set to address its functions in meiosis. Similar to mitosis, Set depletion caused chromosome alignment and cohesion defects. We found that Set is required for accurate error correction by localizing Aurora B/C, and for efficient cleavage of the meiosis-specific Cohesin subunit Rec8 by Separase. Paired chromosomes and sister chromatids were often incompletely separated, likely a primary cause of missegregation. Set performed both its roles in a Sgo2-dependent manner, but, unexpectedly, independently of interaction with PP2A-B56. In line with a role of Set as a Histone chaperone, accumulation of phosphorylated Histone H1 in Set knock-out oocytes occurs concomitantly with reduction of oocyte-specific H1foo on chromosome arms, indicating that Set is required to create the optimal chromatin environment for efficient Rec8 cleavage by Separase in meiosis.
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BibTeX
@misc{keating2026mediates,
title = {{Set mediates chromosome alignment and Cohesin cleavage independently of direct PP2A-B56-binding in oocyte meiosis}},
author = {Leonor Keating and Arianna Esposito Verza and Warif El Yakoubi and Yulia Gryaznova and Safia El Jailani and Damien Cladière and Sandra Touati and Eulalie Buffin and Christophe Rachez and Varvara Sarli and Alberto Pendás and Wei Gu and Andrea Musacchio and Katja Wassmann},
howpublished = {BioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.20.745968},
url = {https://hal.science/hal-05747463v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Set mediates chromosome alignment and Cohesin cleavage independently of direct PP2A-B56-binding in oocyte meiosis
AU - Leonor Keating
AU - Arianna Esposito Verza
AU - Warif El Yakoubi
AU - Yulia Gryaznova
AU - Safia El Jailani
AU - Damien Cladière
AU - Sandra Touati
AU - Eulalie Buffin
AU - Christophe Rachez
AU - Varvara Sarli
AU - Alberto Pendás
AU - Wei Gu
AU - Andrea Musacchio
AU - Katja Wassmann
PY - 2026
DA - 2026/08/21
PB - BioRxiv
DO - 10.64898/2026.08.20.745968
UR - https://hal.science/hal-05747463v1
AB - Set promotes cohesion removal in mitosis by evicting phosphorylated Histone H1 and counteracting Sgo1. In addition, Set promotes chromosome alignment by counteracting Aurora B activation. The underlying molecular mechanisms through which Set performs these activities remain insufficiently characterized, but roles of Set as a Histone chaperone and PP2A inhibitor have been proposed. Building on our previous observations that Set promotes pericentromeric Cohesin removal in oocyte meiosis II, we generated an oocyte-specific conditional knock-out of Set to address its functions in meiosis. Similar to mitosis, Set depletion caused chromosome alignment and cohesion defects. We found that Set is required for accurate error correction by localizing Aurora B/C, and for efficient cleavage of the meiosis-specific Cohesin subunit Rec8 by Separase. Paired chromosomes and sister chromatids were often incompletely separated, likely a primary cause of missegregation. Set performed both its roles in a Sgo2-dependent manner, but, unexpectedly, independently of interaction with PP2A-B56. In line with a role of Set as a Histone chaperone, accumulation of phosphorylated Histone H1 in Set knock-out oocytes occurs concomitantly with reduction of oocyte-specific H1foo on chromosome arms, indicating that Set is required to create the optimal chromatin environment for efficient Rec8 cleavage by Separase in meiosis.
SN - 2692-8205
ER -