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0This research article investigates the behavior of TEAD1, a Hippo pathway transcription factor, in renal cell carcinoma and other cancer cells. The study reveals that TEAD1 forms biomolecular condensates at pericentromeric heterochromatin, which are distinct from typical transcription sites. Unlike smaller condensates that facilitate gene expression, these micrometre-sized depots are transcriptionally inactive and serve to store excess protein. Utilizing high-resolution imaging and genomic sequencing, the authors demonstrate that these clusters are seeded by DNA-binding interactions at clustered MCAT motifs. Disruption of these storage sites leads to an increase in YAP-TEAD target gene expression, suggesting a regulatory role in buffering transcriptional activity. Ultimately, the findings provide a new framework for understanding how nuclear organization contributes to transcriptional dysregulation in tumors.
References:
Wang Y, Liang J, Lange K S, et al. TEAD1 condensates are transcriptionally inactive storage sites on the pericentromeric heterochromatin in cancer cells[J]. Nature Cell Biology, 2026: 1-16.
