Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer Journal Article uri icon



  • AbstractCancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the mechanisms underlying the formation of these pathological networks remain poorly understood. Through a pan-cancer epigenomic analysis, we found that primate-specific endogenous retroviruses (ERVs) are a rich source of enhancers displaying cancer-specific activity. In colorectal cancer and other epithelial tumors, oncogenic AP1/MAPK signaling drives the activation of enhancers derived from the primate-specific ERV family LTR10. Functional studies in colorectal cancer cells revealed that LTR10 elements regulate tumor-specific expression of multiple genes associated with tumorigenesis, such asATG12andXRCC4. Within the human population, individual LTR10 elements exhibit germline and somatic structural variation resulting from a highly mutable internal tandem repeat region, which affects AP1 binding activity. Our findings reveal that ERV-derived enhancers contribute to transcriptional dysregulation in response to oncogenic signaling and shape the evolution of cancer-specific regulatory networks.

publication date

  • October 30, 2021

has restriction

  • green

Date in CU Experts

  • November 9, 2021 3:16 AM

Full Author List

  • Ivancevic A; Simpson DM; Joyner OM; Bagby SM; Nguyen LL; Bitler BG; Pitts TM; Chuong EB

author count

  • 8

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