Mohan Nivedhitha, Dashwood Roderick H, Rajendran Praveen
Center for Epigenetics & Disease Prevention, Texas A&M Health, Houston, TX 77030, USA.
Department of Translational Medical Sciences, Antibody & Biopharmaceuticals Core, Texas A&M School of Medicine, Houston, TX 77030, USA.
Cancers (Basel). 2024 Mar 9;16(6):1104. doi: 10.3390/cancers16061104.
Epigenetic 'reader' proteins, which have evolved to interact with specific chromatin modifications, play pivotal roles in gene regulation. There is growing interest in the alternative splicing mechanisms that affect the functionality of such epigenetic readers in cancer etiology. The current review considers how deregulation of epigenetic processes and alternative splicing events contribute to pathophysiology. An A-Z guide of epigenetic readers is provided, delineating the antagonistic 'yin-yang' roles of full-length versus spliced isoforms, where this is known from the literature. The examples discussed underscore the key contributions of epigenetic readers in transcriptional regulation, early development, and cancer. Clinical implications are considered, offering insights into precision oncology and targeted therapies focused on epigenetic readers that have undergone alternative splicing events during disease pathogenesis. This review underscores the fundamental importance of alternative splicing events in the context of epigenetic readers while emphasizing the critical need for improved understanding of functional diversity, regulatory mechanisms, and future therapeutic potential.
表观遗传“读取器”蛋白已经进化到可与特定的染色质修饰相互作用，在基因调控中发挥关键作用。人们对影响此类表观遗传读取器在癌症病因学中功能的可变剪接机制越来越感兴趣。本综述探讨了表观遗传过程和可变剪接事件的失调如何导致病理生理学变化。本文提供了一份表观遗传读取器的字母指南，描述了全长异构体与剪接异构体的拮抗“阴阳”作用，这些作用在文献中是已知的。所讨论的例子强调了表观遗传读取器在转录调控、早期发育和癌症中的关键作用。本文还考虑了临床意义，为精准肿瘤学和针对在疾病发病过程中发生可变剪接事件的表观遗传读取器的靶向治疗提供了见解。本综述强调了可变剪接事件在表观遗传读取器背景下的根本重要性，同时强调了更好地理解功能多样性、调控机制和未来治疗潜力的迫切需求。
