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TitleZincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression.
Journal, issue, pagesScience, Vol. 389, Issue 6755, Page eadv2861, Year 2025
Publish dateJul 3, 2025
AuthorsDaniëlle Bianchi / Razvan Borza / Erica De Zan / Guizela Huelsz-Prince / Sebastian Gregoricchio / Marleen Dekker / Alex Fish / Abdelghani Mazouzi / Lona J Kroese / Simon Linder / Miguel Hernandez-Quiles / Michiel Vermeulen / Patrick H N Celie / Paul Krimpenfort / Ji-Ying Song / Wilbert Zwart / Lodewyk Wessels / Sebastian M B Nijman / Anastassis Perrakis / Thijn R Brummelkamp /
PubMed AbstractZinc 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 ...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.
External linksScience / PubMed:40608935
MethodsEM (single particle)
Resolution3.16 - 3.26 Å
Structure data

52226

9hjt

EMDB-52226, PDB-9hjt:
Structure of Zincore (SEPHS1:QRICH1) binding to ZFP91 on DNA
Method: EM (single particle) / Resolution: 3.26 Å

52227

9hju

EMDB-52227, PDB-9hju:
Structure of 2x Zincore (SEPHS1:QRICH1) binding to ZFP91 on DNA
Method: EM (single particle) / Resolution: 3.16 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / Zincore Complex / Transcriptional regulator complex / SEPHS1 / Selenide / water dikinase 1 / selenophosphate synthetase 1 / QRICH1 / Zinc finger protein / ZFP91 / Transcription factor

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