TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation.
TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation.
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DOI：
10.1016/j.neuron.2013.08.032
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发表时间：
2013-09-18
期刊：
影响因子：
16.2
通讯作者：
Sweatt JD
中科院分区：
文献类型：
--
作者：
Kaas GA;Zhong C;Eason DE;Ross DL;Vachhani RV;Ming GL;King JR;Song H;Sweatt JD
5-甲基胞嘧啶（5 mC）的动态变化与巩固记忆的关键基因表达的调节有关。然而，人们对5 mC的这些变化在成人大脑中是如何调节的知之甚少。酶泰特甲基胞嘧啶双加氧酶1（TET 1）已被证明可以促进神经系统中的活性DNA去甲基化。因此，我们采取了一种病毒介导的方法，在海马中过表达这种酶，并测试其在记忆形成中的潜在参与。我们发现Tet 1是一个神经元活性调节基因，它的过度表达会导致全局修饰胞嘧啶水平的变化。此外，TET 1或催化失活突变体（TET 1 m）的表达导致了几个神经元记忆相关基因的上调和背景恐惧记忆受损。总之，我们发现神经元Tet 1调节DNA甲基化水平，并且其表达独立于其催化活性，调节CNS活性依赖性基因的表达和记忆形成。
Dynamic changes in 5-methylcytosine (5mC) have been implicated in the regulation of gene expression critical for consolidation of memory. However, little is known about how these changes in 5mC are regulated in the adult brain. The enzyme Tet methylcytosine dioxygenase 1 (TET1) has been shown to promote active DNA demethylation in the nervous system. Therefore, we took a viral-mediated approach to overexpress the enzyme in the hippocampus and test its potential involvement in memory formation. We found that Tet1 is a neuronal-activity regulated gene and that its overexpression leads to changes in global modified cytosine levels. Furthermore, expression of TET1 or a catalytically inactive mutant (TET1m) resulted in the up-regulation of several neuronal memory-associated genes and impaired contextual fear memory. In summary, we show that neuronal Tet1 regulates DNA methylation levels and that its expression, independent of its catalytic activity, regulates the expression of CNS activity- dependent genes and memory formation.
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影响因子：
64.5
作者：
Rai K;Huggins IJ;James SR;Karpf AR;Jones DA;Cairns BR
通讯作者：
Cairns BR
皮质DNA甲基化保持遥远的记忆。
影响因子：
25
作者：
Miller, Courtney A.;Gavin, Cristin F.;White, Jason A.;Parrish, R. Ryley;Honasoge, Avinash;Yancey, Christopher R.;Rivera, Ivonne M.;Rubio, Maria D.;Rumbaugh, Gavin;Sweatt, J. David
通讯作者：
Sweatt, J. David
影响因子：
64.5
作者：
Bhutani N;Burns DM;Blau HM
通讯作者：
Blau HM
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：
4.7
作者：
James, AB;Conway, AM;Morris, BJ
通讯作者：
Morris, BJ