An AP endonuclease functions in active DNA demethylation and gene imprinting in Arabidopsis [corrected].
An AP endonuclease functions in active DNA demethylation and gene imprinting in Arabidopsis [corrected].
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DOI：
10.1371/journal.pgen.1004905
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发表时间：
2015-01
期刊：
影响因子：
4.5
通讯作者：
Zhu JK
中科院分区：
文献类型：
--
作者：
Li Y;Córdoba-Cañero D;Qian W;Zhu X;Tang K;Zhang H;Ariza RR;Roldán-Arjona T;Zhu JK
植物中的主动DNA去甲基化通过碱基切除修复发生，从5-甲基胞嘧啶DNA糖基化酶的ROS 1/DME亚家族去除甲基化胞嘧啶开始。动物体内的主动DNA去甲基化需要DNA糖基化酶TDG或MBD 4，它们分别在5-甲基胞嘧啶氧化或脱氨基后发挥作用。然而，很少有人知道的步骤后，DNA糖基化酶的行动在积极的DNA去甲基化途径在植物和动物。我们在这里表明，拟南芥APE 1 L蛋白具有脱嘌呤/脱嘧啶核酸内切酶的活性和功能下游的ROS 1和DME。APE 1 L和ROS 1在体外相互作用并在体内共定位。ape 1 l突变体植物的全基因组亚硫酸氢盐测序揭示了DNA甲基化的广泛改变。我们发现ape 1 l/zdp双突变体显示胚胎致死性。值得注意的是，ape 1 l +/−zdp−/−突变体显示出母体效应致死表型。APE 1 L和DNA磷酸酶ZDP是FWA和MEA基因在胚乳中印迹所必需的，并且对种子发育很重要。因此，APE 1 L是主动DNA去甲基化途径的一个新组分，与ZDP一起调节拟南芥中的基因印迹。DNA胞嘧啶甲基化（5-methylcytosine，5-meC）是一种重要的表观遗传标记，在发育和生殖过程中，甲基化模式受甲基化和去甲基化反应的协调控制。在植物中，沉默修复酶（ROS 1）是一种具有良好特性的5-meC DNA糖基化酶，通过5-meC切除启动活性DNA去甲基化。我们的前期工作表明，在拟南芥中，一种3′-DNA磷酸酶ZDP在活性DNA去甲基化过程中位于ROS 1的下游。在这里，我们发现，脱嘌呤/脱嘧啶核酸内切酶APE 1 L的功能下游的ROS 1在ZDP独立的分支的活性DNA去甲基化途径在拟南芥。在植物中，基因印迹需要5-meC DNA糖基化酶Demeter（DME），该酶被认为启动了雌配子体中央细胞中主动DNA去甲基化的碱基切除修复途径。然而，除了DME，没有其他的碱基切除修复酶已被发现是重要的基因印迹。我们的研究结果表明，APE 1 L和ZDP共同作用下游的DME调节基因印迹在植物中，并建议DME启动主动DNA去甲基化在中央细胞和胚乳使用APE和ZDP依赖的机制。
Active DNA demethylation in plants occurs through base excision repair, beginning with removal of methylated cytosine by the ROS1/DME subfamily of 5-methylcytosine DNA glycosylases. Active DNA demethylation in animals requires the DNA glycosylase TDG or MBD4, which functions after oxidation or deamination of 5-methylcytosine, respectively. However, little is known about the steps following DNA glycosylase action in the active DNA demethylation pathways in plants and animals. We show here that the Arabidopsis APE1L protein has apurinic/apyrimidinic endonuclease activities and functions downstream of ROS1 and DME. APE1L and ROS1 interact in vitro and co-localize in vivo. Whole genome bisulfite sequencing of ape1l mutant plants revealed widespread alterations in DNA methylation. We show that the ape1l/zdp double mutant displays embryonic lethality. Notably, the ape1l+/−zdp−/− mutant shows a maternal-effect lethality phenotype. APE1L and the DNA phosphatase ZDP are required for FWA and MEA gene imprinting in the endosperm and are important for seed development. Thus, APE1L is a new component of the active DNA demethylation pathway and, together with ZDP, regulates gene imprinting in Arabidopsis. DNA cytosine methylation (5-methylcytosine, 5-meC) is an important epigenetic mark, and methylation patterns are coordinately controlled by methylation and demethylation reactions during development and reproduction. In plants, REPRESSOR OF SILENCING (ROS1) is one of the well characterized 5-meC DNA glycosylases that initiate active DNA demethylation by 5-meC excision. Our previous work showed that a 3′-DNA phosphatase, ZDP, functions downstream of ROS1 during active DNA demethylation in Arabidopsis. Here we found that the apurinic/apyrimidinic endonuclease APE1L functions downstream of ROS1 in a ZDP-independent branch of the active DNA demethylation pathway in Arabidopsis. In plants, gene imprinting requires the 5-meC DNA glycosylase Demeter (DME) that has been proposed to initiate a base excision repair pathway for active DNA demethylation in the central cell in female gametophyte. However, besides DME, no other base excision repair enzymes have been found to be important for gene imprinting. Our results show that APE1L and ZDP act jointly downstream of DME to regulate gene imprinting in plants, and suggest that DME-initiated active DNA demethylation in the central cell and endosperm uses both APE- and ZDP-dependent mechanisms.
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影响因子：
64.5
作者：
Calarco JP;Borges F;Donoghue MT;Van Ex F;Jullien PE;Lopes T;Gardner R;Berger F;Feijó JA;Becker JD;Martienssen RA
通讯作者：
Martienssen RA
影响因子：
64.5
作者：
Pontes, Olga;Li, Carey Fei;Pikaard, Craig S.
通讯作者：
Pikaard, Craig S.
影响因子：
4.8
作者：
Isabel Martinez-Macias, Maria;Cordoba-Canero, Dolores;Roldan-Arjona, Teresa
通讯作者：
Roldan-Arjona, Teresa
影响因子：
3.7
作者：
Joldybayeva, Botagoz;Prorok, Paulina;Saparbaev, Murat
通讯作者：
Saparbaev, Murat
DOI：
10.1126/science.1224839
发表时间：
2012-09-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ibarra CA;Feng X;Schoft VK;Hsieh TF;Uzawa R;Rodrigues JA;Zemach A;Chumak N;Machlicova A;Nishimura T;Rojas D;Fischer RL;Tamaru H;Zilberman D
通讯作者：
Zilberman D