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MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data
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MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data
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Journal Article
MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data
2024
Overview
Aberrations in the capacity of DNA/chromatin modifiers and transcription factors to bind non-coding regions can lead to changes in gene regulation and impact disease phenotypes. However, identifying distal regulatory elements and connecting them with their target genes remains challenging. Here, we present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover cis regulatory elements (CREs) in a 1 Mb region around every promoter in the genome. MethNet identifies clusters of highly ranked CREs, referred to as ‘hubs’, which contribute to the regulation of multiple genes and significantly affect patient survival. Promoter-capture Hi-C confirmed that highly ranked associations involve physical interactions between CREs and their gene targets, and CRISPR interference based single-cell RNA Perturb-seq validated the functional impact of CREs. Thus, MethNet-identified CREs represent a valuable resource for unraveling complex mechanisms underlying gene expression, and for prioritizing the verification of predicted non-coding disease hotspots.
Epigenetic aberrations can affect gene regulation and impact diseases, but understanding these regulatory connections remains challenging. Here, the authors present MethNet, a pipeline to integrate DNA methylation and gene expression profiles across multiple cancers to uncover distal cis-regulatory element hubs and their functional impact.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
