5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging.
5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging.
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DOI：
10.1038/nn.2959
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发表时间：
2011-10-30
影响因子：
25
通讯作者：
Jin P
中科院分区：
文献类型：
--
作者：
Szulwach KE;Li X;Li Y;Song CX;Wu H;Dai Q;Irier H;Upadhyay AK;Gearing M;Levey AI;Vasanthakumar A;Godley LA;Chang Q;Cheng X;He C;Jin P
DNA甲基化动力学影响大脑功能，并在神经系统疾病中改变。5-羟甲基胞嘧啶（5-hmC）是一种衍生自5-甲基胞嘧啶的DNA碱基，占大脑中修饰胞嘧啶的约40%，并与DNA甲基化相关的可塑性有关。我们在三个不同年龄的小鼠海马和小脑中绘制了5-hmC全基因组，这使我们能够评估其在出生后神经发育到成年期间的稳定性和动态调节。我们发现在神经元细胞中5-hmC的发育程序性获得。5-hmC调控区域的表观基因组定位显示在神经发育和衰老过程中稳定和动态修饰的位点。通过对人小脑5-hmC基因的分析，我们发现了5-hmC基因组的保守特征。最后，我们发现5-hmC水平与甲基-CpG结合蛋白2剂量呈负相关，甲基-CpG结合蛋白2是一种由突变引起Rett综合征的基因编码的蛋白质。这些数据表明，5-hmC介导的表观遗传修饰在神经发育和疾病中至关重要。
DNA methylation dynamics influence brain function and are altered in neurological disorders. 5-hydroxymethylcytosine (5-hmC), a DNA base that is derived from 5-methylcytosine, accounts for ~40% of modified cytosine in the brain and has been implicated in DNA methylation–related plasticity. We mapped 5-hmC genome-wide in mouse hippocampus and cerebellum at three different ages, which allowed us to assess its stability and dynamic regulation during postnatal neurodevelopment through adulthood. We found developmentally programmed acquisition of 5-hmC in neuronal cells. Epigenomic localization of 5-hmC–regulated regions revealed stable and dynamically modified loci during neurodevelopment and aging. By profiling 5-hmC in human cerebellum, we found conserved genomic features of 5-hmC. Finally, we found that 5-hmC levels were inversely correlated with methyl-CpG–binding protein 2 dosage, a protein encoded by a gene in which mutations cause Rett syndrome. These data suggest that 5-hmC–mediated epigenetic modification is critical in neurodevelopment and diseases.
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影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
3.5
作者：
Collins, AL;Levenson, JM;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
56.9
作者：
Hellman, Asaf;Chess, Andrew
通讯作者：
Chess, Andrew