SEgene identifies links between super enhancers and gene expression across cell types

Abstract Enhancers are non-coding DNA regions that facilitate gene transcription, with a specialized subset, super-enhancers, known to exert exceptionally strong transcriptional activation effects. Super-enhancers have been implicated in oncogenesis, and their identification is achievable through hi...

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Main Authors: Norio Shinkai, Ken Asada, Hidenori Machino, Ken Takasawa, Satoshi Takahashi, Nobuji Kouno, Masaaki Komatsu, Ryuji Hamamoto, Syuzo Kaneko
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Systems Biology and Applications
Online Access:https://doi.org/10.1038/s41540-025-00533-x
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Summary:Abstract Enhancers are non-coding DNA regions that facilitate gene transcription, with a specialized subset, super-enhancers, known to exert exceptionally strong transcriptional activation effects. Super-enhancers have been implicated in oncogenesis, and their identification is achievable through histone mark chromatin immunoprecipitation followed by sequencing data using existing analytical tools. However, conventional super-enhancer detection methodologies often do not accurately reflect actual gene expression levels, and the large volume of identified super-enhancers complicates comprehensive analysis. To address these limitations, we developed the super-enhancer to gene links (SE-to-gene Links) analysis, a platform named “SEgene” which incorporates the peak-to-gene links approach—a statistical method designed to reveal correlations between genes and peak regions ( https://github.com/hamamoto-lab/SEgene ). This platform enables a targeted evaluation of super-enhancer regions in relation to gene expression, facilitating the identification of super-enhancers that are functionally linked to transcriptional activity. Here, we demonstrate the application of SE-to-gene Links analysis to public datasets, confirming its efficacy in accurately detecting super-enhancers and identifying functionally associated genes. Additionally, SE-to-gene Links analysis identified ERBB2 as a significant gene of interest in the lung adenocarcinoma dataset from the National Cancer Center Japan cohort, suggesting a potential impact across multiple patient samples. Thus, the SE-to-gene Links analysis provides an analytical tool for evaluating super-enhancers as potential therapeutic targets, supporting the identification of clinically significant super-enhancer regions and their functionally associated genes.
ISSN:2056-7189