The role of histone post-translational modifications (PTMs) in chromatin structure and genome function has been the subject of intense debate for more than 60 years. Though complex, the discourse can be summarized in two distinct — and deceptively simple — questions: What is the function of histone PTMs? And how should they be studied? Decades of research show these queries are intricately linked and far from straightforward. Here we provide a historical perspective, highlighting how the arrival of new technologies shaped discovery and insight. Despite their limitations, the tools available at each period had a profound impact on chromatin research, and provided essential clues that advanced our understanding of histone PTM function. Finally, we discuss recent advances in the application of defined nucleosome substrates, the study of multivalent chromatin interactions, and new technologies driving the next era of histone PTM research.

中文翻译：

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超越尾部：组蛋白翻译后修饰和染色质研究中背景的后果

60 多年来，组蛋白翻译后修饰 (PTM) 在染色质结构和基因组功能中的作用一直是激烈争论的话题。尽管很复杂，但该讨论可以概括为两个截然不同且看似简单的问题：组蛋白 PTM 的功能是什么？以及应该如何研究它们？数十年的研究表明，这些查询错综复杂地联系在一起，而且远非直截了当。在这里，我们提供了一个历史视角，强调了新技术的到来如何塑造发现和洞察力。尽管存在局限性，但每个时期可用的工具都对染色质研究产生了深远的影响，并为增进我们对组蛋白 PTM 功能的理解提供了重要线索。最后，我们讨论了确定的核小体底物的应用、多价染色质相互作用的研究以及推动下一个组蛋白 PTM 研究时代的新技术方面的最新进展。