转录沉默是基因表达调控的重要方式,它对于保持细胞的不同分化状态和维持染色质的稳定性至关重要。沉默信息调节因子2(silent information regulator 2,Sir2)参与酵母交配型基因沉默(silentmating type)、端粒区基因沉默以及核糖体DNA(r...转录沉默是基因表达调控的重要方式,它对于保持细胞的不同分化状态和维持染色质的稳定性至关重要。沉默信息调节因子2(silent information regulator 2,Sir2)参与酵母交配型基因沉默(silentmating type)、端粒区基因沉默以及核糖体DNA(rDNA)沉默。端粒区的基因沉默可能是酵母衰老过程中的机制之一,处于沉默状态的染色质中的许多基因无转录活性,可能由此影响酵母生长。展开更多
DNA的大部分区域通过包装成特殊的染色质结构而失去活性称为染色质沉默。这些特殊的染色质结构在维持染色体结构稳定和基因调控中起重要作用。有实验表明,沉默染色质的组蛋白H3和H4的的氨基末端尾部相对于基因组的其他区域是低乙酰化的...DNA的大部分区域通过包装成特殊的染色质结构而失去活性称为染色质沉默。这些特殊的染色质结构在维持染色体结构稳定和基因调控中起重要作用。有实验表明,沉默染色质的组蛋白H3和H4的的氨基末端尾部相对于基因组的其他区域是低乙酰化的。组蛋白去乙酰化酶SIR2(silent information regulator2)是参与染色质沉默的一种重要的蛋白质。SIR2具有两种相关联的酶活性,组蛋白去乙酰化酶活性和NAD高能骨架的断裂活性,并在酶反应过程中产生一种新的产物氧代乙酰基ADP核糖基(O-acetyl-ADP-ribose)。SIR2的组蛋白去乙酰化酶活性为研究SIR2与沉默染色质的组蛋白低乙酰化状态的关系提供了直接证据。而SIR2的这两种酶活性的关系也表明,组蛋白去乙酰化酶活性不是SIR2惟一的功能。SIR2的NAD水解酶活性和O-acetyl-ADP-ribose的合成过程也可能是染色质沉默机制所必需的。展开更多
Resveratrol(RES),a natural polyphenolic phytochemical,has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer’s disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this...Resveratrol(RES),a natural polyphenolic phytochemical,has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer’s disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this study,we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein(APP),whose duplications and mutations cause familial AD.We found a mild but significant transcriptional increase of Drosophila Sir2(dSir2)by RES supplementation for up to 17 days in APP flies,but not for 7 days.RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies.We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons.Interestingly,RES increased sleep in the absence of dSir2 in dSir2-null mutants,and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies.Finally,we showed that Aβaggregates in APP flies were reduced by RES and dSir2,probably via inhibiting Drosophilaβ-secretase(dBACE).Our data suggest that RES rescues the APP-induced behavioral deficits and Aβburden largely,but not exclusively,via dSir2.展开更多
文摘转录沉默是基因表达调控的重要方式,它对于保持细胞的不同分化状态和维持染色质的稳定性至关重要。沉默信息调节因子2(silent information regulator 2,Sir2)参与酵母交配型基因沉默(silentmating type)、端粒区基因沉默以及核糖体DNA(rDNA)沉默。端粒区的基因沉默可能是酵母衰老过程中的机制之一,处于沉默状态的染色质中的许多基因无转录活性,可能由此影响酵母生长。
文摘DNA的大部分区域通过包装成特殊的染色质结构而失去活性称为染色质沉默。这些特殊的染色质结构在维持染色体结构稳定和基因调控中起重要作用。有实验表明,沉默染色质的组蛋白H3和H4的的氨基末端尾部相对于基因组的其他区域是低乙酰化的。组蛋白去乙酰化酶SIR2(silent information regulator2)是参与染色质沉默的一种重要的蛋白质。SIR2具有两种相关联的酶活性,组蛋白去乙酰化酶活性和NAD高能骨架的断裂活性,并在酶反应过程中产生一种新的产物氧代乙酰基ADP核糖基(O-acetyl-ADP-ribose)。SIR2的组蛋白去乙酰化酶活性为研究SIR2与沉默染色质的组蛋白低乙酰化状态的关系提供了直接证据。而SIR2的这两种酶活性的关系也表明,组蛋白去乙酰化酶活性不是SIR2惟一的功能。SIR2的NAD水解酶活性和O-acetyl-ADP-ribose的合成过程也可能是染色质沉默机制所必需的。
基金funded by grants from the National Natural Science Foundation of China(81970999)the Shanghai Rising-Star Program(19QA1404900)the Innovation Program of the Shanghai Municipal Education Commission(2019-01-07-00-02-E00037).
文摘Resveratrol(RES),a natural polyphenolic phytochemical,has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer’s disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this study,we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein(APP),whose duplications and mutations cause familial AD.We found a mild but significant transcriptional increase of Drosophila Sir2(dSir2)by RES supplementation for up to 17 days in APP flies,but not for 7 days.RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies.We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons.Interestingly,RES increased sleep in the absence of dSir2 in dSir2-null mutants,and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies.Finally,we showed that Aβaggregates in APP flies were reduced by RES and dSir2,probably via inhibiting Drosophilaβ-secretase(dBACE).Our data suggest that RES rescues the APP-induced behavioral deficits and Aβburden largely,but not exclusively,via dSir2.
