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小鼠染色体刚度的细胞周期及与年龄相关的调节

Cell cycle and Age-Related Modulations of Mouse Chromosome Stiffness.

作者信息

Liu Ning, Qiang Wenan, Jordan Philip, Marko John F, Qiao Huanyu

机构信息

Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Center for Developmental Therapeutics, Northwestern University, Evanston, IL, USA.

出版信息

bioRxiv. 2025 Mar 10:2024.03.06.583771. doi: 10.1101/2024.03.06.583771.

DOI:10.1101/2024.03.06.583771
PMID:38559262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10979861/
Abstract

Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a ten-fold increase in stiffness (Young's modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle, and by age-related factors.

摘要

染色体结构复杂，染色体组织的许多方面仍不为人所知。测量染色体的刚度能为其结构特性提供有价值的见解。在本研究中，我们分析了减数第一次分裂中期（MI）和减数第二次分裂中期（MII）卵母细胞染色体的刚度。我们的结果显示，与体细胞染色体相比，MI染色体的刚度（杨氏模量）增加了十倍。此外，发现MII染色体的刚度低于MI染色体。我们研究了减数分裂特异性黏连蛋白复合体在调节染色体刚度中的作用。令人惊讶的是，来自三个减数分裂特异性黏连蛋白突变体的染色体刚度与野生型染色体的刚度没有显著差异，这表明这些黏连蛋白可能不是染色体刚度的主要决定因素。此外，我们的研究结果显示，MI卵母细胞的染色体刚度随年龄增长而增加。由于衰老与DNA损伤水平升高有关，我们研究了依托泊苷诱导的DNA损伤对染色体刚度的影响，发现它导致MI卵母细胞的刚度降低。总体而言，我们的研究强调了染色体刚度的动态和周期性本质，它受到细胞周期和与年龄相关因素的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/30c98b81233d/nihpp-2024.03.06.583771v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/306b65657a65/nihpp-2024.03.06.583771v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/5d00b73b2301/nihpp-2024.03.06.583771v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/11834b404153/nihpp-2024.03.06.583771v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/d84455fa0305/nihpp-2024.03.06.583771v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/30c98b81233d/nihpp-2024.03.06.583771v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/306b65657a65/nihpp-2024.03.06.583771v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/5d00b73b2301/nihpp-2024.03.06.583771v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/11834b404153/nihpp-2024.03.06.583771v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/d84455fa0305/nihpp-2024.03.06.583771v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24bb/11956641/30c98b81233d/nihpp-2024.03.06.583771v3-f0005.jpg

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本文引用的文献

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Meiosis: Dances Between Homologs.减数分裂：同源染色体的舞蹈。
Annu Rev Genet. 2023 Nov 27;57:1-63. doi: 10.1146/annurev-genet-061323-044915. Epub 2023 Oct 3.
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Epigenetic regulation of aging: implications for interventions of aging and diseases.衰老的表观遗传学调控：干预衰老和疾病的意义。
Signal Transduct Target Ther. 2022 Nov 7;7(1):374. doi: 10.1038/s41392-022-01211-8.
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Distinct and diverse chromatin proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions.衰老小鼠器官中独特而多样的染色质蛋白质组揭示了与生理功能相关的蛋白质特征。
Elife. 2022 Mar 8;11:e73524. doi: 10.7554/eLife.73524.
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Etoposide-induced DNA damage is increased in p53 mutants: identification of ATR and other genes that influence effects of p53 mutations on Top2-induced cytotoxicity.依托泊苷诱导的 DNA 损伤在 p53 突变体中增加：鉴定影响 p53 突变对拓扑异构酶 2 诱导细胞毒性的 ATR 和其他基因。
Oncotarget. 2022 Feb 14;13:332-346. doi: 10.18632/oncotarget.28195. eCollection 2022.
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HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics.HP1α 是一种染色质交联剂，可控制核和有丝分裂染色体力学。
Elife. 2021 Jun 9;10:e63972. doi: 10.7554/eLife.63972.
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The central role of DNA damage in the ageing process.DNA 损伤在衰老过程中的核心作用。
Nature. 2021 Apr;592(7856):695-703. doi: 10.1038/s41586-021-03307-7. Epub 2021 Apr 28.
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Mitotic chromosomes.有丝分裂染色体。
Semin Cell Dev Biol. 2021 Sep;117:7-29. doi: 10.1016/j.semcdb.2021.03.014. Epub 2021 Apr 6.
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Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis.联会复合体二聚化调控减数分裂中染色体的排列和交叉模式。
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Genes Dev. 2020 Dec 1;34(23-24):1562-1564. doi: 10.1101/gad.345488.120.