Notch controls APC/C <sup>FZR-1</sup> to enable accumulation of chromatin regulators in germline stem cells from <i>Caenorhabditis elegans</i>

Originally known for its function in the cell cycle, the anaphase-promoting complex/cyclosome (APC/C) also plays a crucial role in regulating differentiation and maintaining cell identity. However, the mechanisms by which APC/C mediates developmental processes are not fully understood. In this study, we show that APC/C and its activator FZR-1 regulate the chromatin regulators MES-4 and MES-3. These proteins are part of histone methylation complexes essential for maintaining germline stem cell (GSC) identity in the germ line of <i>Caenorhabditis elegans</i>. APC/C<sup>FZR-1</sup> facilitates the degradation of MES-4 and MES-3 when GSCs transition toward differentiating into oocytes. The activity of APC/C<sup>FZR-1</sup> is restricted by the Notch signaling pathway provided by the distal tip cell, which is responsible for maintaining the stemness of the GSC pool. This negative regulation enables the accumulation of MES-3 and MES-4 in GSCs, offering an additional component by which niche activity modulates the <i>C. elegans</i> germ line.

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Publication Details

Journal
Science Advances
Published
2025-05-30
DOI
https://doi.org/10.1126/sciadv.adu8572
Primary Topic
Genetics, Aging, and Longevity in Model Organisms
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article
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article

Notch controls APC/C FZR-1 to enable accumulation of chromatin regulators in germline stem cells from Caenorhabditis elegans

D.T. Puerta, Judith Kimble, Susan Strome, Adrián Fragoso-Luna et al.
Science Advances
Genetics, Aging, and Longevity in Model Organisms
article

Notch controls APC/C FZR-1 to enable accumulation of chromatin regulators in germline stem cells from Caenorhabditis elegans

D.T. Puerta, Judith Kimble, Susan Strome, Adrián Fragoso-Luna, José Pérez‐Martín, Sarah L. Crittenden, Sara Rivera-Martín
article en

Abstract

Originally known for its function in the cell cycle, the anaphase-promoting complex/cyclosome (APC/C) also plays a crucial role in regulating differentiation and maintaining cell identity. However, the mechanisms by which APC/C mediates developmental processes are not fully understood. In this study, we show that APC/C and its activator FZR-1 regulate the chromatin regulators MES-4 and MES-3. These proteins are part of histone methylation complexes essential for maintaining germline stem cell (GSC) identity in the germ line of <i>Caenorhabditis elegans</i>. APC/C<sup>FZR-1</sup> facilitates the degradation of MES-4 and MES-3 when GSCs transition toward differentiating into oocytes. The activity of APC/C<sup>FZR-1</sup> is restricted by the Notch signaling pathway provided by the distal tip cell, which is responsible for maintaining the stemness of the GSC pool. This negative regulation enables the accumulation of MES-3 and MES-4 in GSCs, offering an additional component by which niche activity modulates the <i>C. elegans</i> germ line.

Science AdvancesVol. 11(22)
University of Wisconsin–Madison (US), University of California, Santa Cruz (US), Instituto de Biomedicina de Valencia (ES), Instituto de Biología Funcional y Genómica (ES)
Openalex Percentile: Top 90%
Genetics, Aging, and Longevity in Model Organisms
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