Epigenetic mechanisms in mammals.

Epigenetic mechanisms in mammals.
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DOI:
10.1007/s00018-008-8432-4
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发表时间:
2009-02
影响因子:
8
通讯作者:
Pradhan, S.
Pradhan, S.
中科院分区:
生物学1区
文献类型:
--
作者:
Kim, J. K.;Samaranayake, M.;Pradhan, S.

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DNA和组蛋白甲基化在哺乳动物中是连锁的,并受到有丝分裂遗传的影响。然而,甲基化是如何在连续的细胞分裂之间传播和维持的还没有完全了解。已经发现了一系列可以将甲基化标记添加到胞嘧啶核碱基以及赖氨酸和精氨酸氨基酸残基的酶家族。除了甲基转移酶,还有组蛋白修饰酶和辅助蛋白,它们可以促进和/或靶向表观遗传标记。最近发现了几种赖氨酸和精氨酸脱甲基酶,并推测哺乳动物细胞中存在活性DNA脱甲基酶。哺乳动物甲基DNA结合蛋白MBD 2和从头DNA甲基转移酶DNMT 3A和DNMT 3B经实验证明具有DNA去甲基化酶活性。因此,复杂的哺乳动物表观遗传机制似乎是动态的,但沿着一组精心设计的事件,发生在哺乳动物的发展过程中可逆的。
DNA and histone methylation are linked and subjected to mitotic inheritance in mammals. Yet how methylation is propagated and maintained between successive cell divisions is not fully understood. A series of enzyme families that can add methylation marks to cytosine nucleobases, and lysine and arginine amino acid residues has been discovered. Apart from methyltransferases, there are also histone modification enzymes and accessory proteins, which can facilitate and/or target epigenetic marks. Several lysine and arginine demethylases have been discovered recently, and the presence of an active DNA demethylase is speculated in mammalian cells. A mammalian methyl DNA binding protein MBD2 and de novo DNA methyltransferase DNMT3A and DNMT3B are shown experimentally to possess DNA demethylase activity. Thus, complex mammalian epigenetic mechanisms appear to be dynamic yet reversible along with a well-choreographed set of events that take place during mammalian development.
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