MethNet: a robust approach to identify regulatory hubs and their distal targets from cancer data
Year: 2024
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: Drug resistant pathways in relapsed acute lymphoblastic leukemia (ALL), G2103664672, G4038528566, G7145547518, G8065436493, G838546163, Cancer Center Support Grant, The impact of changes in chromatin architecture on cancer phenotypes and tumor progression, Nuclear organization and its role in gene regulation, Dynamic 3D chromatin remodeling in acute leukemia - Resubmission - 1
OpenAlex ID: W4400781620