Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer [RNA-seq]
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ABSTRACT: Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the processes that configure these pathological networks remain poorly understood. Through a pan-cancer epigenomic analysis, we found that primate-specific endogenous retroviruses (ERVs) are an abundant source of enhancers that mediate transcriptional dysregulation in cancer. In colorectal cancer and other epithelial tumors, AP1 signaling drives aberrant activation of enhancers derived from the primate-specific ERV family LTR10. CRISPR studies revealed that LTR10 elements control colorectal cancer-specific gene expression at multiple loci associated with tumorigenesis. Within the human population, individual LTR10 elements show extensive structural variation due to repeat instability of an internal variable number tandem repeat (VNTR) region that affects AP1 binding. Our findings reveal that ERV-derived enhancers link oncogenic signaling to transcriptional dysregulation and shape the evolution of cancer-specific regulatory networks.
ORGANISM(S): Homo sapiens
PROVIDER: GSE186618 | GEO | 2021/10/31
REPOSITORIES: GEO
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