Reduction in DNA methyltransferases and alteration of DNA methylation pattern associate with mouse skin ageing
Reduction in DNA methyltransferases and alteration of DNA methylation pattern associate with mouse skin ageing
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DOI：
10.1111/exd.12375
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发表时间：
2014-05-01
影响因子：
3.6
通讯作者：
Xu, Xiangru
中科院分区：
文献类型：
--
作者：
Qian, Hong;Xu, Xiangru
了解皮肤衰老的分子机制对于开发有效的抗衰老策略至关重要。最近，有研究表明表观遗传学可能与组织衰老和年龄相关疾病有关;然而，关于皮肤衰老的证据非常有限。我们在小鼠皮肤中进行了一项初步研究，通过定量RT-PCR和甲基化DNA免疫沉淀（MeDIP）芯片来测试DNA甲基转移酶（Dnmts），DNA去甲基化酶如10 - 11易位酶（Tets）和基因启动子的DNA甲基化是否随年龄而变化。我们发现Dnmt 3a、Dnmt 3b和Tet 2的表达随着皮肤老化而显著下降。全基因组DNA甲基化分析表明，基因启动子区存在高甲基化和低甲基化。这些基因的功能分类表明，细胞增殖抑制和免疫反应的激活可能是皮肤老化引起的重要适应。这些发现为皮肤衰老的表观遗传调控提供了新的线索。
Understanding molecular mechanisms of skin ageing is critical for developing effective anti-ageing strategies. Recently, it has been suggested that epigenetics maybe be involved in tissue ageing and age-related diseases; however, the evidence regarding skin ageing has been very limited. We ran a pilot study in mouse skin to test whether DNA methyltransferases (Dnmts), DNA demethylases such as ten-eleven translocation enzymes (Tets) and DNA methylation of gene promoters change with age by quantitative RT-PCR and methylated DNA immunoprecipitation (MeDIP)-chip. We discovered that the expression of Dnmt3a, Dnmt3b and Tet2 declines significantly with skin ageing. The genome-wide DNA methylation analysis indicates that both hypermethylation and hypomethylation in promoters of genes are taken place. Functional category of those genes suggests that inhibition of cell proliferation and activation of immune response are important adaptations likely induced by skin ageing. These findings shed new light on epigenetic regulation of skin ageing.