Work

Enhancer RNA-mediated gene regulation as a novel therapeutic strategy for autoimmune diseases 2527

Year: 2025

Type: article

Abstract: Description Understanding gene expression regulation is crucial for therapeutic target discovery. Although enhancer RNAs (eRNAs) are implicated in regulation, their exact mechanisms remain unclear. We analyzed ChIP-seq and RNA-seq data to identify enhancers activated by LPS stimulation, confirming eRNA expression. ABC score analysis identified a specific enhancer regulating TNF-α and LT-α. To validate this enhancer’s function, we generated knockout mice targeting this region, observing modulation of TNF-α and LT-α expression. Using antisense oligonucleotides (ASOs) against eRNAs further confirmed their regulatory roles. Targeting eRNAs in rheumatoid arthritis (RA) and psoriasis mouse models showed disease amelioration. Notably, the this super-enhancer is conserved in humans, and ASO targeting in PBMCs from RA patients modulated TNF-α and LT-α expression. Lastly, we cataloged immune-response super-enhancer regions and associated eRNAs, offering therapeutic targets. Funding Sources This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (NRF-2023R1A2C1005804, RS-2024-00408822, RS-2024-00461521) Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.433

Authors: Min Jeong Cho, Su Min Kim, Hyo Jin Park, Wonjin Woo, Lark Kyun Kim

Institution: Yonsei University

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Research Foundation, National Research Foundation of Korea, Ministry of Science and ICT, South Korea