Histone proteins are decorated with numerous post-(PTMs) or co-(CTMs) translational modifications mainly on their unstructured tails, but also on their globular domain. For many decades research on histone modifications has been focused almost solely on the biological role of modifications occurring at the side-chain of internal amino acid residues. In contrast, modifications on the terminal N-alpha amino group of histones—despite being highly abundant and evolutionarily conserved—have been largely overlooked. This oversight has been due to the fact that these marks were being considered inert until recently, serving no regulatory functions. However, during the past few years accumulating evidence has drawn attention towards the importance of chemical marks added at the very N-terminal tip of histones and unveiled their role in key biological processes including aging and carcinogenesis. Further elucidation of the molecular mechanisms through which these modifications are regulated and by which they act to influence chromatin dynamics and DNA-based processes like transcription is expected to enlighten our understanding of their emerging role in controlling cellular physiology and contribution to human disease. In this review, we clarify the difference between N-alpha terminal (Nt) and internal (In) histone modifications; provide an overview of the different types of known histone Nt-marks and the associated histone N-terminal transferases (NTTs); and explore how they function to shape gene expression, chromatin architecture and cellular phenotypes.

中文翻译：

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组蛋白N-alpha末端修饰：尾巴末端的基因组调控。

组蛋白主要在其非结构化尾巴上以及在其球状结构域上修饰有许多后（PTMs）或co-（CTMs）翻译修饰。几十年来，对组蛋白修饰的研究几乎只集中在内部氨基酸残基侧链发生的修饰的生物学作用上。相反，对组蛋白的末端N-α氨基的修饰（尽管高度丰富且在进化上是保守的）已被大大忽略。造成这种疏忽的原因是，直到最近这些标记仍被认为是惰性的，没有任何监管功能。然而，在过去的几年中，越来越多的证据引起人们对在组蛋白N末端添加化学标记的重要性的关注，并揭示了它们在关键生物过程（包括衰老和致癌性）中的作用。进一步阐明调控这些修饰的分子机制，以及它们通过其影响染色质动力学和基于DNA的过程（如转录）的分子机制，有望启发我们对其在控制细胞生理和人类疾病中的作用的认识。在这篇综述中，我们阐明了N-alpha末端（Nt）和内部（In）组蛋白修饰之间的区别；提供已知组蛋白Nt标记的不同类型以及相关的组蛋白N末端转移酶（NTT）的概述；