Over the past two decades, it has become increasingly clear that spatiotemporal regulation of gene transcription (i.e., epigenetics) and message translation (i.e., epitranscriptomics) are paramount in orchestrating cell fate decisions in ontogeny, hematopoiesis, inflammatory and immune responses, and a host of other vital aspects of normal physiology. Over the same period, it has also become strikingly clear that these critical control mechanisms are commonly dysregulated in a spectrum of human diseases.(1−3) At the molecular level, discriminant gating of gene transcription is achieved through a combinatorial repertoire of covalent and noncovalent modifications to chromatin—the assembly of chromosomal DNA and histone proteins that define the architectural form of our genomes. Site-specific modifications of both DNA and histone proteins collectively influence chromatin conformation to activate or repress transcription at individual gene locations. Once transcription is completed, the resultant pre-mRNA is elaborated by the splicesome complex to form the mature mRNA that is to be translated into cellular proteins. Controlled variation of splicing adds significantly to the diversity of protein forms required for cellular structure and function.(4) Beyond splicing, it is now clear the pre-mRNA, mRNA, and other RNA forms are—like chromatin—susceptible to myriad site-specific covalent and noncovalent modifications; these modifications control many aspects of RNA biology, from cellular localization to mRNA lifetime and the like.(5−7) In humans over 100 specific modifications to RNA have been identified,(7,8) and these site-specific RNA modifications have been shown to play critical roles in the discriminant gating of mRNA translation, as well as in a variety of other RNA biology control mechanisms. It is easy to see how dysregulation of these fine-tuned, transcription and translation gating mechanisms can lead to human diseases. In light of this, the chemical biology and medicinal chemistry communities have responded with an impressive array of chemical modulators of the enzymes and binding proteins that control different aspects of chromatin- and RNA-modification. In the case of chromatin-modification, a number of these molecules have clear therapeutic potential and have hence progressed to clinical testing and, in a few cases, FDA approval as new medicines. Chemical modulation of RNA-modifying proteins is in a more nascent state of development but nonetheless also holds great promise for novel therapeutic agents. In many ways, however, we have only scratched the proverbial surface of this vast opportunity for novel therapeutics. For this reason, ACS Medicinal Chemistry Letters, together with ACS Chemical Biology, ACS Chemical Neuroscience, ACS Infectious Diseases, ACS Pharmacology& Translational Science, and Journal of Medicinal Chemistry are devoting special issues to this important area. The ACS Medicinal Chemistry Letters special issue will be dedicated to advances in our understanding of chemical modulators of chromatin- and RNA-modifications and will accept manuscripts in the form of Notes, Letters, Innovations, and Technology Notes. We call upon scientists in medicinal chemistry and allied fields to contribute their research and innovations to this special issue of the journal. Guest Editor, Robert A. Copeland (Accent Therapeutics, Inc.) and Associate Editor Donna Huryn will be working closely to produce this special issue and to publish it in early 2022. All participating journals invite submissions to the joint special issue: ACS Chemical Biology invites submissions that use chemical biology approaches or devise chemical biology tools to understand or exploit epigenetic modifications. ACS ChemicalNeuroscience will focus on epigenetic mechanisms associated with neurogenesis, neural plasticity, as well as cognition and memory. Papers of interest also include those aimed at neuropsychiatric disorders for which epigenetic deregulation is a key driver of disease phenotype. ACS Infectious Diseases would like to encourage manuscripts that investigate epigenetic mechanisms that can offer some insights toward the development of an infectious diseases either by affecting the survival, replication, or infection capacity of the pathogen or the response from the host. ACS Pharmacology& TranslationalScience will focus on epigenetic biomarkers—both preclinical development and clinical application—in cancer and CNS disorders. The Journal of Medicinal Chemistry would like to encourage submissions across the full spectrum of epigenetics, including epigenetic studies focused on human and nonhuman species.(9) The deadline for manuscript submission is June 30, 2021. Manuscripts can be submitted to the journal via https://acsparagonplus.acs.org and selecting the topic “Epigenetics: Targeting Chromatin- and RNA-Modifications” in the drop-down menu. Presubmission inquiries are welcome and can be sent to [email protected]. Please review the Author Guidelines for more information about the journal and guidance for manuscript preparation. Views expressed in this editorial are those of the authors and not necessarily the views of the ACS. This article references 9 other publications.

中文翻译：

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表观遗传学特刊：靶向染色质和 RNA 修饰

在过去的二十年里，越来越清楚的是，基因转录（即表观遗传学）和信息翻译（即，表观转录组学）的时空调控对于协调个体发育、造血、炎症和免疫反应以及宿主的细胞命运决定至关重要。正常生理学的其他重要方面。在同一时期，这些关键控制机制在一系列人类疾病中通常失调也变得非常清楚。（1-3）在分子水平上，基因转录的判别门控是通过共价和染色质的非共价修饰——染色体 DNA 和组蛋白的组装，定义了我们基因组的结构形式。DNA 和组蛋白的位点特异性修饰共同影响染色质构象以激活或抑制单个基因位置的转录。一旦转录完成，产生的前体 mRNA 就会被剪接体复合物加工成成熟的 mRNA，然后将其翻译成细胞蛋白质。剪接的受控变异显着增加了细胞结构和功能所需的蛋白质形式的多样性。 (4) 除了剪接之外，现在很清楚前体 mRNA、mRNA 和其他 RNA 形式——就像染色质一样——对无数位点敏感——特定的共价和非共价修饰；这些修饰控制着 RNA 生物学的许多方面，从细胞定位到 mRNA 寿命等。(5-7) 在人类中，已经确定了超过 100 种对 RNA 的特定修饰，(7, 8) 并且这些位点特异性 RNA 修饰已被证明在 mRNA 翻译的判别门控以及各种其他 RNA 生物学控制机制中发挥着关键作用。很容易看出这些微调的转录和翻译门控机制的失调如何导致人类疾病。有鉴于此，化学生物学和药物化学界以一系列令人印象深刻的酶和结合蛋白的化学调节剂做出回应，这些调节剂控制染色质和 RNA 修饰的不同方面。在染色质修饰的情况下，这些分子中有许多具有明显的治疗潜力，因此已进入临床试验，在少数情况下，FDA 批准作为新药。RNA 修饰蛋白的化学调节处于更初级的发展状态，但对于新型治疗剂也有很大的希望。然而，在许多方面，我们只是触及了这个新疗法的巨大机会的众所周知的表面。为此原因，ACS Medicinal Chemistry Letters与ACS Chemical Biology、ACS Chemical Neuroscience、ACS Infectious Diseases、ACS Pharmacology & Translational Science和Journal of Medicinal Chemistry一起致力于这个重要领域的特殊问题。在ACS药物化学快报特刊将致力于我们对染色质和 RNA 修饰的化学调节剂的理解的进展，并将接受笔记、信函、创新和技术笔记形式的手稿。我们呼吁药物化学和相关领域的科学家为该杂志的这一特刊贡献他们的研究和创新。客座编辑 Robert A. Copeland（Accent Therapeutics, Inc.）和副主编 Donna Huryn 将密切合作，共同制作这期特刊，并于 2022 年初出版。所有参与期刊都邀请向联合特刊投稿：ACS Chemical Biology邀请使用化学生物学方法或设计化学生物学工具来理解或利用表观遗传修饰的提交。ACS化学神经科学将关注与神经发生、神经可塑性以及认知和记忆相关的表观遗传机制。感兴趣的论文还包括那些针对神经精神疾病的论文，其中表观遗传失调是疾病表型的关键驱动因素。ACS Infectious Diseases希望鼓励研究表观遗传机制的手稿，这些机制可以通过影响病原体的存活、复制或感染能力或宿主的反应，为传染病的发展提供一些见解。ACS 药理学与转化科学将专注于癌症和中枢神经系统疾病的表观遗传生物标志物——包括临床前开发和临床应用。这Journal of Medicinal Chemistry 欢迎所有表观遗传学领域的投稿，包括针对人类和非人类物种的表观遗传研究。(9) 投稿截止日期为 2021 年 6 月 30 日。手稿可通过 https 提交给期刊： //acsparagonplus.acs.org 并在下拉菜单中选择主题“表观遗传学：靶向染色质和 RNA 修饰”。欢迎提交预提交查询，并可发送至[email protected]。请查看作者指南以获取有关该期刊的更多信息和手稿准备指南。本社论中表达的观点是作者的观点，不一定代表 ACS 的观点。本文引用了 9 篇其他出版物。