The frequency of aneuploid gamete formation increases with maternal age,yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood.Using the multicellular orga...The frequency of aneuploid gamete formation increases with maternal age,yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood.Using the multicellular organism Caenorhabditis elegans,we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors.Point mutations in the head domain of the cohesin component SMC-1,which alter local hydrophobicity,cause meiotic defects that vary with age.A severe mutation causes incomplete synapsis and defective crossover formation,and a minor one causes age-related diakinesis bivalent abnormalities.Notably,while the mild mutation causes defects only in aged worms,worms with the severe mutation exhibit significantly alleviated phenotypes with age.Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase,which restores impaired cohesin loading.These findings reveal that cohesin variants,meiotic progression speed during early prophase,and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.展开更多
DNA甲基化和组蛋白修饰是表观遗传学中调控基因表达的两个重要方式。泛素样含PHD和环指域蛋白1(ubiquitin like with PHD and ring finger domains1,UHRF1)是一种多结构域的核蛋白,通过其特殊的结构域将DNA甲基化与组蛋白修饰联系起来,...DNA甲基化和组蛋白修饰是表观遗传学中调控基因表达的两个重要方式。泛素样含PHD和环指域蛋白1(ubiquitin like with PHD and ring finger domains1,UHRF1)是一种多结构域的核蛋白,通过其特殊的结构域将DNA甲基化与组蛋白修饰联系起来,参与基因转录调控。UHRF1在肝脏、肠、大脑等多个器官的生理功能状态调控及器官发育中发挥重要作用,此外其还参与机体的免疫反应和肿瘤发生。UHRF1缺陷的胚胎显示全基因组DNA甲基化水平显著降低,表明其在维持DNA甲基化方面中起着重要作用。展开更多
基金supported by grants from the National Natural Science Foundation of China(32370780 and 32022018)the National Key Research and Development Program of China(2021YFA1101001)+1 种基金the Taishan Scholars Program Special FundSome strains were provided by the CGC,which is funded by NIH Office of Research Infrastructure Programs(P40 OD010440).
文摘The frequency of aneuploid gamete formation increases with maternal age,yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood.Using the multicellular organism Caenorhabditis elegans,we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors.Point mutations in the head domain of the cohesin component SMC-1,which alter local hydrophobicity,cause meiotic defects that vary with age.A severe mutation causes incomplete synapsis and defective crossover formation,and a minor one causes age-related diakinesis bivalent abnormalities.Notably,while the mild mutation causes defects only in aged worms,worms with the severe mutation exhibit significantly alleviated phenotypes with age.Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase,which restores impaired cohesin loading.These findings reveal that cohesin variants,meiotic progression speed during early prophase,and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.
文摘DNA甲基化和组蛋白修饰是表观遗传学中调控基因表达的两个重要方式。泛素样含PHD和环指域蛋白1(ubiquitin like with PHD and ring finger domains1,UHRF1)是一种多结构域的核蛋白,通过其特殊的结构域将DNA甲基化与组蛋白修饰联系起来,参与基因转录调控。UHRF1在肝脏、肠、大脑等多个器官的生理功能状态调控及器官发育中发挥重要作用,此外其还参与机体的免疫反应和肿瘤发生。UHRF1缺陷的胚胎显示全基因组DNA甲基化水平显著降低,表明其在维持DNA甲基化方面中起着重要作用。
