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Genome-wide analysis of enhancer landscape in colorectal cancer subgroups (RNA-seq)

ABSTRACT: Colorectal cancer (CRC) is a highly malignant solid tumor and causes millions of cancer related death worldwide. Here, using H3K27ac chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with gene expression data (RNA-seq), we describe the active cis-regulatory landscape across more than seventy diverse CRC patient tissues, including tumor and native tissue. Analysis of the enhancers and super-enhancers with recurrently gained or lost activity revealed novel, clinically relevant insights into CRC biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors which is responsible for tumorigenesis and the maintenance of normal intestinal function. Genomic studies have revealed four distinct consensus molecular subgroups (CMS) with divergent biology and clinical behavior and we reveal that differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity. Our integrated analysis of enhancer elements in a large series of CRC patient paired samples reveals novel insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156451 | GEO | 2021/08/26

REPOSITORIES: GEO

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Genome-wide analysis of enhancer landscape in colorectal cancer subgroups (ChIP-seq)

Project description:Colorectal cancer (CRC) is a highly malignant solid tumor and causes millions of cancer related death worldwide. Here, using H3K27ac chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with gene expression data (RNA-seq), we describe the active cis-regulatory landscape across more than seventy diverse CRC patient tissues, including tumor and native tissue. Analysis of the enhancers and super-enhancers with recurrently gained or lost activity revealed novel, clinically relevant insights into CRC biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors which is responsible for tumorigenesis and the maintenance of normal intestinal function. Genomic studies have revealed four distinct consensus molecular subgroups (CMS) with divergent biology and clinical behavior and we reveal that differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity. Our integrated analysis of enhancer elements in a large series of CRC patient paired samples reveals novel insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.

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Transcriptional super-enhancers connected to cell identity and disease

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