Functions of intrinsic disorder in proteins involved in DNA demethylation during pre-implantation embryonic development
Functions of intrinsic disorder in proteins involved in DNA demethylation during pre-implantation embryonic development
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植入前胚胎发育过程中参与 DNA 去甲基化的蛋白质内在紊乱的功能
DOI：
10.1016/j.ijbiomac.2019.06.143
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发表时间：
2019-09-01
影响因子：
8.2
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Han, Chengquan;Cui, Chenchen;Zhang, Yong
DNA去甲基化参与了哺乳动物着床前胚胎发育的许多生物学过程。到目前为止，DNA去甲基化的复杂机制仍不完全清楚。10 - 11易位家族（TET 3、TET 1和TET 2）、胸腺嘧啶DNA糖基化酶（TDG）和DNA甲基转移酶1（DNMT 1）被认为是着床前胚胎DNA去甲基化的主要蛋白酶。TET 3、TET 1、TET 2、TDG和DNMT 1含有丰富水平的内在无序蛋白质区域（IDPR），其有助于增加蛋白质的功能多样性。因此，我们试图从内在障碍的角度来探讨复杂的DNA去甲基化在植入前胚胎。这五种生物大分子都具有与DNA去甲基化相关的功能结构域。它们可以通过复杂的蛋白质-蛋白质相互作用网络共同完成植入前胚胎的DNA去甲基化。内在无序分析结果表明，这些蛋白质是部分内在无序蛋白。IDPR中存在许多可识别的基于无序的DNA结合位点、蛋白质结合位点和翻译后修饰位点，以及DNA去甲基化缺陷点突变，可显著改变这些蛋白质的局部无序倾向。据我们所知，这项工作为研究哺乳动物植入前胚胎发育过程中DNA甲基化重编程的机制提供了一个新的视角。(C)2019 Elsevier B. V.版权所有。
DNA demethylation is involved in many biological processes during pre-implantation embryonic development in mammals. To date, the complicated mechanism of DNA demethylation is still not fully understood. Ten-eleven translocation family (TET3, TETI and TET2), thymine DNA glycosylase (TDG) and DNA methyltransferase 1 (DNMT1) are considered the major protein enzymes of DNA demethylation in pre-implantation embryos. TET3, TETI, TET2, TDG, and DNMT1 contain abundant levels of intrinsically disordered protein regions (IDPRs), which contribute to increasing the functional diversity of proteins. Thus we tried to explore the complicated DNA demethylation in pre-implantation embryos from the intrinsic disorder perspective. These five biological macromolecules all have DNA demethylation-related functional domains. They can work together to fulfill DNA demethylation in pre-implantation embryos through complex protein-protein interaction networks. Intrinsic disorder analysis results showed these proteins were partial intrinsically disordered proteins. Many identifiable disorder-based DNA-binding sites, protein-binding sites and post-translational modification sites located in the intrinsically disordered regions, and DNA demethylation deficiency point mutations in the IDPRs could significantly change the local disorder propensity of these proteins. To the best of our knowledge, this work provides a new viewpoint for studying the mechanism of DNA methylation reprogramming during mammalian pre implantation embryonic development. (C) 2019 Elsevier B.V. All rights reserved.