New Histone Lysine Acylation Biomarkers and Their Roles in Epigenetic Regulation
New Histone Lysine Acylation Biomarkers and Their Roles in Epigenetic Regulation
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DOI：
10.1002/cpz1.746
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发表时间：
2023-04
期刊：
影响因子：
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通讯作者：
Qi-mei Fu;Amber Cat;Y. G. Zheng
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作者：
Qi-mei Fu;Amber Cat;Y. G. Zheng
蛋白质翻译后修饰（PTM）是一种有利于细胞适应动态细胞内和环境条件的生化机制。最近，一些酰化标记已被鉴定为发生在哺乳动物细胞中特定赖氨酸残基上的新蛋白质 PTM：异丁酰化、甲基丙烯酸化、苯甲酰化、异烟酰化和乳酰化。这些酰化标记最初被发现出现在核小体组蛋白上，但它们也可能作为非组蛋白上的普遍生物标志物出现。这些 PTM 的存在是代谢的下游结果，表明活性细胞代谢物与蛋白质功能调节之间存在密切的串扰。新出现的证据表明，组蛋白上的这些酰化标记会影响 DNA 转录，并且在功能上与经过充分研究的赖氨酸乙酰化不同。在这里，我们讨论这些酰化的酶调节和代谢病因学、识别不同酰化的“阅读器”蛋白以及它们可能的生理和病理功能。其中一些修饰与其他经过充分研究的酰化相关，并微调基因表达的调节。总的来说，这些酰化标记的发现揭示了代谢和表观遗传学之间新的分子联系，并为未来的研究提出了许多问题。 © 2023 作者。当前协议由 Wiley periodicals LLC 出版。
Protein posttranslational modification (PTM) is a biochemical mechanism benefitting cellular adaptation to dynamic intracellular and environmental conditions. Recently, several acylation marks have been identified as new protein PTMs occurring on specific lysine residues in mammalian cells: isobutyrylation, methacrylation, benzoylation, isonicotinylation, and lactylation. These acylation marks were initially discovered to occur on nucleosomal histones, but they potentially occur as prevalent biomarkers on non‐histone proteins as well. The existence of these PTMs is a downstream consequence of metabolism and demonstrates the intimate crosstalk between active cellular metabolites and regulation of protein function. Emerging evidence indicates that these acylation marks on histones affect DNA transcription and are functionally distinct from the well‐studied lysine acetylation. Herein, we discuss enzymatic regulation and metabolic etiology of these acylations, 'reader' proteins that recognize different acylations, and their possible physiological and pathological functions. Several of these modifications correlate with other well‐studied acylations and fine‐tune the regulation of gene expression. Overall, findings of these acylation marks reveal new molecular links between metabolism and epigenetics and open up many questions for future investigation. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.