O'Brown Zach Klapholz, Greer Eric Lieberman
Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Adv Exp Med Biol. 2022;1389:177-210. doi: 10.1007/978-3-031-11454-0_8.
Chromatin, consisting of deoxyribonucleic acid (DNA) wrapped around histone proteins, facilitates DNA compaction and allows identical DNA code to confer many different cellular phenotypes. This biological versatility is accomplished in large part by post-translational modifications to histones and chemical modifications to DNA. These modifications direct the cellular machinery to expand or compact specific chromatin regions and mark certain regions of the DNA as important for cellular functions. While each of the four bases that make up DNA can be modified (Iyer et al., Prog Mol Biol Transl Sci. 101:25-104, 2011), this chapter will focus on methylation of the 6th position on adenines (6mA). 6mA is a prevalent modification in unicellular organisms and until recently was thought to be restricted to them. A flurry of conflicting studies have proposed that 6mA either does not exist, is present at low levels, or is present at relatively high levels and regulates complex processes in different multicellular eukaryotes. Here, we will briefly describe the history of 6mA, examine its evolutionary conservation, and evaluate the current methods for detecting 6mA. We will discuss the proteins that have been reported to bind and regulate 6mA and examine the known and potential functions of this modification in eukaryotes. Finally, we will close with a discussion of the ongoing debate about whether 6mA exists as a directed DNA modification in multicellular eukaryotes.
染色质由缠绕在组蛋白周围的脱氧核糖核酸（DNA）组成，它有助于DNA压缩，并使相同的DNA编码赋予许多不同的细胞表型。这种生物学上的多功能性在很大程度上是通过对组蛋白的翻译后修饰和对DNA的化学修饰来实现的。这些修饰引导细胞机制扩展或压缩特定的染色质区域，并将DNA的某些区域标记为对细胞功能很重要。虽然构成DNA的四种碱基中的每一种都可以被修饰（Iyer等人，《分子生物学与转化科学进展》。101:25 - 104，2011），但本章将重点关注腺嘌呤第6位的甲基化（6mA）。6mA在单细胞生物中是一种普遍的修饰，直到最近人们还认为它仅限于单细胞生物。一系列相互矛盾的研究表明，6mA要么不存在，要么含量很低，要么含量相对较高并调节不同多细胞真核生物中的复杂过程。在这里，我们将简要描述6mA的历史，研究其进化保守性，并评估目前检测6mA的方法。我们将讨论据报道与6mA结合并调节6mA的蛋白质，并研究这种修饰在真核生物中的已知和潜在功能。最后，我们将以关于6mA在多细胞真核生物中是否作为一种定向DNA修饰存在的持续争论作为结尾进行讨论。
