5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels
5-Hydroxymethylation marks a class of neuronal gene regulated by intragenic methylcytosine levels
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DOI：
10.1016/j.ygeno.2014.08.013
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发表时间：
2014-11-01
期刊：
影响因子：
4.4
通讯作者：
Walsh, Colum P.
中科院分区：
文献类型：
--
作者：
Irwin, Rachelle E.;Thakur, Avinash;Walsh, Colum P.
我们最近发现了一类神经元基因，它从母亲那里继承了高水平的基因内甲基化，并在以后的发育过程中保持这种甲基化。我们在这里表明，这些基因涉及基本的神经元功能，如突触后信号，而不是神经元的发育和继承高水平的5mC，但不是5hmC，从母亲。5mC分布在整个基因体中，似乎有助于转录，因为在DNA甲基转移酶I（Dnmt 1）敲除的胚胎干细胞以及用甲基转移酶抑制剂处理的成纤维细胞中转录减少。然而，在成年人的大脑中，转录与5hmC的增加更密切相关，这在没有可测量的5mC损失的情况下发生。这些发现增加了越来越多的证据表明，5mC可能在促进转录中发挥作用，以及其在基因沉默中的经典作用。(C)2014爱思唯尔公司All rights reserved.
We recently identified a class of neuronal gene inheriting high levels of intragenic methylation from the mother and maintaining this through later development. We show here that these genes are implicated in basic neuronal functions such as post-synaptic signalling, rather than neuronal development and inherit high levels of 5mC, but not 5hmC, from the mother. 5mC is distributed across the gene body and appears to facilitate transcription, as transcription is reduced in DNA methyltransferase I (Dnmt1) knockout embryonic stem cells as well as in fibroblasts treated with a methyltransferase inhibitor. However in adult brain, transcription is more closely associated with a gain in 5hmC, which occurs without a measurable loss of 5mC. These findings add to growing evidence that there may be a role for 5mC in promoting transcription as well as its classical role in gene silencing. (C) 2014 Elsevier Inc. All rights reserved.