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DNA 甲基化的特异性或非特异性募集，一个表观遗传学困境。

Specific or not specific recruitment of DNMTs for DNA methylation, an epigenetic dilemma.

机构信息

INSERM unit 1098, University of Bourgogne Franche-Comté, Besançon, France.

EPIGENExp (EPIgenetics and GENe EXPression Technical Platform), Besançon, France.

出版信息

Clin Epigenetics. 2018 Feb 9;10:17. doi: 10.1186/s13148-018-0450-y. eCollection 2018.

DOI:10.1186/s13148-018-0450-y
PMID:29449903
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5807744/
Abstract

Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes. For example, the DNMT3L/DNMT3A complex is mainly related to de novo DNA methylation in embryonic states, whereas the DNMT1/PCNA/UHRF1 complex is required for maintaining global DNA methylation following DNA replication. On the opposite to these unspecific DNA methylation machineries (no preferential DNA sequence), some recently identified DNMT-including complexes are recruited on specific DNA sequences. The coexistence of both types of DNA methylation (un/specific) suggests a close cooperation and an orchestration between these systems to maintain genome and epigenome integrities. Deregulation of these systems can lead to pathologic disorders.

摘要

我们目前对 DNA 甲基化过程的认识正在发生重大变化：首先，即使人们普遍承认 DNMT3A 和 DNMT3B 与从头甲基化有关，而 DNMT1 与 DNA 甲基化的遗传有关，但这些区别现在并不那么明显。其次，自十年前以来，许多 DNMT 的合作伙伴已经参与了 DNA 甲基化活性的调节以及 DNMT 在 DNA 上的募集。相互作用的多样性以及这些相互作用的结合使我们能够对不同的包含 DNMT 的复合物进行分类。例如，DNMT3L/DNMT3A 复合物主要与胚胎状态下的从头 DNA 甲基化有关，而 DNMT1/PCNA/UHRF1 复合物则需要在 DNA 复制后维持全局 DNA 甲基化。与这些非特异性 DNA 甲基化机制（没有优先的 DNA 序列）相反，最近鉴定出的一些包含 DNMT 的复合物被募集到特定的 DNA 序列上。这两种类型的 DNA 甲基化（非/特异性）的共存表明这些系统之间存在密切的合作和协调，以维持基因组和表观基因组的完整性。这些系统的失调可能导致病理紊乱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/7a0489658e12/13148_2018_450_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/394df7deffe8/13148_2018_450_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/05ca13bb09dd/13148_2018_450_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/fcfda57c04f4/13148_2018_450_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/4cbbf7dcbe51/13148_2018_450_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/cd4dbd974403/13148_2018_450_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/7a0489658e12/13148_2018_450_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/394df7deffe8/13148_2018_450_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/05ca13bb09dd/13148_2018_450_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/fcfda57c04f4/13148_2018_450_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/4cbbf7dcbe51/13148_2018_450_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/cd4dbd974403/13148_2018_450_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/5807744/7a0489658e12/13148_2018_450_Fig6_HTML.jpg

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