Hou Huihui, Qiu Yueqi, Zhao Ming
School of Public Health, Nanjing Medical University, Nanjing, China.
Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China.
Clin Rev Allergy Immunol. 2025 Aug 27;68(1):84. doi: 10.1007/s12016-025-09096-5.
In the intricate regulation of gene expression, multiple regulatory elements play crucial roles. Among these, enhancers stand out as important elements that can boost the activity of promoters and make target genes more likely to be transcribed. Recent studies have revealed that sequence variations and gene rearrangements in enhancer regions could disrupt enhancer-promoter interactions, contributing to disease susceptibility and developmental abnormalities. Enhancer dysregulation is associated with numerous pathological conditions, spanning malignancies, autoimmune diseases, cardiovascular pathologies, and neurodegenerative ailments. Although the advent of high-throughput sequencing has enabled comprehensive enhancer profiling across the genome, elucidating their precise functional mechanisms continues to pose significant challenges. This review summarizes the structural features, identification methodologies, transcriptional regulatory mechanisms, and pathogenic contributions of enhancers in autoimmune diseases. Furthermore, we highlight emerging enhancer-based therapeutic strategies, offering novel insights for the targeted treatment of immune-related disorders. Additionally, we explore the role of phase separation in enhancer regulation and its potential association with autoimmune pathogenesis, proposing phase separation modulation as a promising therapeutic avenue.
在基因表达的复杂调控中，多种调控元件发挥着关键作用。其中，增强子作为重要元件脱颖而出，它能够增强启动子的活性，使靶基因更有可能被转录。最近的研究表明，增强子区域的序列变异和基因重排可能会破坏增强子与启动子的相互作用，导致疾病易感性和发育异常。增强子失调与多种病理状况相关，包括恶性肿瘤、自身免疫性疾病、心血管疾病和神经退行性疾病。尽管高通量测序技术的出现使得能够对全基因组进行全面的增强子分析，但阐明其精确的功能机制仍然面临重大挑战。本综述总结了增强子在自身免疫性疾病中的结构特征、鉴定方法、转录调控机制和致病作用。此外，我们强调了基于增强子的新兴治疗策略，为免疫相关疾病的靶向治疗提供了新的见解。此外，我们探讨了相分离在增强子调控中的作用及其与自身免疫发病机制的潜在关联，提出相分离调控作为一种有前景的治疗途径。
