Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India.
Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India.
Prog Mol Biol Transl Sci. 2023;197:261-302. doi: 10.1016/bs.pmbts.2023.01.011. Epub 2023 Mar 6.
Developmental proceedings and maintenance of cellular homeostasis are regulated by the precise orchestration of a series of epigenetic events that eventually control gene expression. DNA methylation and post-translational modifications (PTMs) of histones are well-characterized epigenetic events responsible for fine-tuning gene expression. PTMs of histones bear molecular logic of gene expression at chromosomal territory and have become a fascinating field of epigenetics. Nowadays, reversible methylation on histone arginine and lysine is gaining increasing attention as a significant PTM related to reorganizing local nucleosomal structure, chromatin dynamics, and transcriptional regulation. It is now well-accepted and reported that histone marks play crucial roles in colon cancer initiation and progression by encouraging abnormal epigenomic reprogramming. It is becoming increasingly clear that multiple PTM marks at the N-terminal tails of the core histones cross-talk with one another to intricately regulate DNA-templated biological processes such as replication, transcription, recombination, and damage repair in several malignancies, including colon cancer. These functional cross-talks provide an additional layer of message, which spatiotemporally fine-tunes the overall gene expression regulation. Nowadays, it is evident that several PTMs instigate colon cancer development. How colon cancer-specific PTM patterns or codes are generated and how they affect downstream molecular events are uncovered to some extent. Future studies would address more about epigenetic communication, and the relationship between histone modification marks to define cellular functions in depth. This chapter will comprehensively highlight the importance of histone arginine and lysine-based methylation modifications and their functional cross-talk with other histone marks from the perspective of colon cancer development.
发育过程和细胞内稳态的维持受一系列表观遗传事件的精确调控，这些事件最终控制基因表达。DNA 甲基化和组蛋白的翻译后修饰（PTMs）是负责微调基因表达的典型表观遗传事件。组蛋白 PTMs 在染色体区域承载着基因表达的分子逻辑，已成为表观遗传学的一个迷人领域。如今，组蛋白精氨酸和赖氨酸上的可逆甲基化作为一种与局部核小体结构、染色质动力学和转录调控重新组织相关的重要 PTM 受到越来越多的关注。现在已经被广泛接受和报道，组蛋白标记通过促进异常的表观基因组重编程，在结肠癌的发生和发展中起着至关重要的作用。越来越明显的是，核心组蛋白 N 端尾部的多个 PTM 标记相互作用，以精细调节多种恶性肿瘤（包括结肠癌）中的 DNA 模板生物过程，如复制、转录、重组和损伤修复。这些功能相互作用提供了一个额外的信息层，时空微调整体基因表达调控。如今，很明显，几种 PTM 引发了结肠癌的发生。结肠癌特异性 PTM 模式或密码是如何产生的，以及它们如何影响下游分子事件，在一定程度上已经被揭示。未来的研究将更多地探讨表观遗传通讯，以及组蛋白修饰标记与定义细胞功能之间的关系。这一章将从结肠癌发展的角度全面强调组蛋白精氨酸和赖氨酸甲基化修饰及其与其他组蛋白标记的功能相互作用的重要性。
