Repeat element–anchored enhancer–promoter interactions (REEPIs) shape the regulatory landscape of hormone-resistant breast cancer
Year: 2026
Type: preprint
Abstract: Repeat elements (REs) comprise over half of the human genome and are increasingly recognized as regulatory components, yet their role in therapy resistance remains unclear. Here, we integrate CAGE and RADICL-seq to map regulatory elements and RNA–chromatin interactions in estrogen receptor– positive breast cancer cells (MCF7) and their long-term estrogen-deprived (LTED) derivatives. We identify repeat element–anchored enhancer–promoter interactions (REEPIs), defined by the presence of annotated REs at both enhancer and promoter sites. In LTED cells, REEPIs are enriched for ERV1 and ERVL elements and involve specific repeat pairings associated with transcription factor combinations such as SP1–SMAD3 and SP1–NFYC. At the gene level, these REEPIs are preferentially linked to genes involved in chromatin remodeling, DNA repair, and lineage plasticity. Our findings reveal a repeat-guided regulatory architecture associated with transcriptional adaptation in endocrine resistance and identify REEPIs as a previously underexplored component of regulatory reprogramming in hormone-resistant breast cancer.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: European Commission, Ministry of Education, Culture, Sports, Science and Technology, Korean Foundation for Cancer Research, Kobayashi Foundation for Cancer Research, Japan Society for the Promotion of Science, RIKEN, Core Research for Evolutional Science and Technology, RIKEN Center for Biosystems Dynamics Research
Awards: ホルモン依存性がんの再発におけるノンコーディングRNAの役割解明, Development of a novel technology to capture RNA-chromatin interactions, Identification of chromatin-associated RNA using long-read sequencing, G3716062013, Elucidation of the mechanism for transcriptional regulation through RNA cloud in endocrine therapy-resistant breast cancer, Finding of functional lncRNAs using newly developed RADCL-IP-seq technology, G544149491, G675968210, G7617532284
OpenAlex ID: W7212231194