真核基因表达在多个层面上进行复杂调控。蛋白编码基因首先在细胞核中以前mRNA形式转录，在被转运到细胞质进行翻译之前，经历一系列的RNA加工步骤。在RNA加工过程中，大部分人类基因（>95%）通过可变剪接方式生成单一基因的多个mRNA亚型，从而有效地增加了基因组的复杂性。由于大多数基因的剪接是共转录发生的，基因表达的调控层次往往相互之间存在功能性的相互作用。在本综述中，我们概述了可变剪接在三个不同层次（受剪接机制、转录过程和染色质结构的调控）上的调控机制，重点强调了表观遗传修饰的调控作用以及这些层次之间的相互作用。具体而言，我们将表观遗传修饰对可变剪接的主要影响分为三种不同类型：通过影响转录速率、剪接因子招募或剪接因子的表达/活性来实现。表观遗传修饰和剪接的失调在癌症中非常常见，我们还讨论了表观遗传改变如何导致剪接失调以及它们的功能后果的潜在机制。我们旨在提供关于不同基因表达层次复杂调控的见解，从而为调控与疾病相关的剪接失调的新方法提供启示。本文归类于以下主题：RNA加工>3'端加工；RNA加工>剪接机制；RNA加工>剪接调控/可变剪接；疾病与发育中的RNA>疾病中的RNA。©2023 Wiley Periodicals LLC.

Eukaryotic gene expression is intricately regulated at multiple levels. The protein-coding genes are first transcribed as pre-mRNAs in the nucleus and undergo a series of RNA processing steps before being transported into the cytoplasm for translation. During RNA processing, most human genes (>95%) undergo alternative splicing to generate multiple mRNA isoforms from a single gene, which effectively diversifies the genome complexity. Since the splicing of most genes occurs co-transcriptionally, the regulation layers of gene expression often show functional interactions with each other. In this review, we provide a brief overview of alternative splicing regulation in three different layers (controlled by the splicing machinery, transcription process, and chromatin structure), emphasizing the regulatory roles of epigenetic modifications and the crosstalk between these layers. Specifically, we categorize the major effects of the epigenetic modifications on alternative splicing into three different types: by affecting transcription rate, splicing factor recruitment, or the expression/activity of splicing factor. The dysregulation of epigenetics and splicing are extremely common in cancer, we also discuss the potential mechanisms of how epigenetic changes can lead to splicing dysregulation and their functional consequences. We aim to provide insights into the complicated regulation of different gene expression layers, which will shed light on the novel approaches to modulate disease-related splicing dysregulation. This article is categorized under: RNA Processing > 3' End Processing RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Disease.© 2023 Wiley Periodicals LLC.