| First Author | Bianchi D | Year | 2025 |
| Journal | Science | Volume | 389 |
| Issue | 6755 | Pages | eadv2861 |
| PubMed ID | 40608935 | Mgi Jnum | J:369749 |
| Mgi Id | MGI:8221322 | Doi | 10.1126/science.adv2861 |
| Citation | Bianchi D, et al. (2025) Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression. Science 389(6755):eadv2861 |
| abstractText | Zinc finger proteins (ZNFs) are the largest family of transcription factors, yet how they activate gene expression remains unclear. In this study, we identified Zincore, a protein complex consisting of QRICH1 and SEPHS1, as a ZNF-specific coregulator essential for embryonic development in mice and associated with developmental syndromes in humans. We also identified ZFP91 as a representative Zincore client, binding the conserved promoter motif CTTTAAR. Cryo-electron microscopy of a Zincore-ZFP91-DNA complex revealed a SEPHS1 arginine clamp to recognize the DNA-bound zinc finger domains. This mode of binding explains recognition of different ZNFs and stabilizes ZFP91 onto its cognate DNA motif. Thus, our study identified Zincore as a ZNF-specific coregulator essential for development, involving a distinctive mechanism that locks ZNFs onto DNA and regulates transcription. |
