齊一生物科技（上海）有限公司
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中國科學報》，這是上項證明動物存在線粒體脅迫適應性跨代遺傳現(xiàn)象的研究，也加深了對跨代遺傳調(diào)控機制的理解。該研究為人類線粒體疾病的遺傳機制研究提供了新思路，在線粒體疾病的遺傳篩選、優(yōu)生、臨床干預及治療手段開發(fā)方面也有潛在的應用價值。
線粒體是細胞中具有重要功能的細胞器。細胞所需能量的 80% 由線粒體供給。細胞對環(huán)境中線粒體脅迫的適應能力對細胞適應環(huán)境、生物個體維持自身生存具有重要意義。為進一步揭示這種現(xiàn)象背后的調(diào)控機制，劉穎團隊對單基因突變的線蟲進行了篩選。結(jié)果發(fā)現(xiàn)線蟲線粒體脅迫耐受性的跨代遺傳受到組蛋白 H3K4me3 修飾和 DNA 腺苷 N6 - 甲基化修飾的調(diào)控。這兩種修飾能夠作為遺傳信息的載體從親代線蟲基因組傳遞到子代線蟲基因組，增強線粒體脅迫適應性相關基因的表達，從而使得子代線蟲對線粒體脅迫更加耐受。
discriminate host genome from invader DNA1. With the recent advent of more sensitive detection techniques, 6mA has also been detected in some eukaryotes2,3,4,5,6,7,8. However, the physiological function of this epigenetic mark in eukaryotes remains elusive. Heritable changes in DNA 5mC methylation have been associated with transgenerational inheritance of responses to a high-fat diet9, thus raising the exciting possibility that 6mA may also be transmitted across generations and serve as a carrier of inheritable information. Using Caenorhabditis elegans as a model, here we report that histone H3K4me3 and DNA 6mA modifications are required for the transmission of mitochondrial stress adaptations to progeny. Intriguingly, the global DNA 6mA level is significantly elevated following mitochondrial perturbation. N6-methyldeoxyadenine marks mitochondrial stress response genes and promotes their transcription to alleviate mitochondrial stress in progeny. These findings suggest that 6mA is a precisely regulated epigenetic mark that modulates stress response and signals transgenerational inheritance in C. elegans.
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