ArticleGenome medicine2025
Characterizing heterogeneous cis-regulatory elements in gene regulatory programs associated with breast cancer.
Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Characterizing heterogeneous cis-regulatory elements in gene regulatory programs associated with breast cancer.Genome medicine · 2025Article
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19 authors.
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Abstract
backgroundCis-regulatory elements (CREs) control oncogene expression and malignant phenotypes. The high clinicopathological heterogeneity of cancer cannot be explained by gene expression alone, being attributed to CRE heterogeneity. However, characterizing cancer-associated CREs is challenging. To address this issue, we performed a single-cell epigenomic analysis of clinical specimens.
methodsTo map the multicellular ecosystem of breast cancer (BC) and identify candidate CREs (cCREs), we performed a single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) of 38 prospectively collected BC samples with various clinicopathological characteristics.
resultsFirst, we performed single-cell chromatin accessibility profiling of a high-quality set of 22,775 cells from BC samples. Cells were annotated using marker gene accessibility and integration with existing single-cell RNA sequencing data. The chromatin accessibility patterns exhibited by cancer cells were consistent with the clinicopathological features of each tumor. We identified 224,585 cCREs across the BC ecosystem. By identifying cluster-specific differentially accessible cCREs (DA-cCREs) and constructing a putative enhancer-promoter network, we mapped the cis-regulatory landscape for cancer cells and the tumor microenvironment. The accessibility of putative enhancers targeting the same gene differed within or between tumors, highlighting intra- and inter-cis-regulatory tumor heterogeneity.
conclusionsThis study provides a valuable resource for future epigenetic research on BC and highlights the diverse regulatory landscape within or among tumor(s), suggesting that cCREs regulate intra- and intertumor heterogeneity.
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