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0This research examines how lineage-determining transcription factors physically reshape chromatin to regulate essential oncogenes through multi-enhancer interactions. Using advanced optical chromatin tracing and protein degradation systems, the authors demonstrate that factors like EBF1 and TCF1 act as permeable barriers to cohesin, a motor protein that loops DNA. By restricting cohesin's movement, these factors promote the local centralization of distant enhancers and promoters within the cell's nucleus. This architectural shift facilitates the simultaneous engagement of multiple regulatory elements at the single-allele level, specifically within gene-sparse hubs critical for cancer cell survival. Ultimately, the study reveals a fundamental mechanism where transcription factors coordinate the three-dimensional folding of the genome to drive oncogenic gene expression.
References:
Zhou Y, Jay A, Burget N, et al. Lineage-determining transcription factors constrain cohesin to drive multi-enhancer oncogene regulation[J]. Nature cell biology, 2026, 28(1): 149-165.
