在这项研究中，研究小组确定了Zincore，一种由QRICH1和SEPHS1组成的蛋白复合物，是小鼠胚胎发育所必需的ZNFs特异性共调节因子，并与人类发育综合征相关。该研究团队还将ZFP91确定为具有代表性的Zincore客户，它结合了保守的启动子基元CTTTAAR。Zincore-ZFP91-DNA复合体的低温电子显微镜显示SEPHS1精氨酸钳可以识别DNA结合的锌指结构域。这种结合模式解释了对不同ZNFs的识别，并将ZFP91稳定在其同源DNA基序上。他们的研究发现，Zincore是一种对发育至关重要的ZNFs特异性共调节剂，涉及一种将ZNFs锁定在DNA上并调节转录的独特机制。
据悉，锌指蛋白（ZNFs）是最大的转录因子家族，但它们如何激活基因表达尚不清楚。
附：英文原文
Title: Zincore, an atypical coregulator, binds zinc finger transcription factors to control gene expression
Author: Danille 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
Issue&Volume: 2025-07-03
Abstract: 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.
DOI: adv2861
Source: https://www.science.org/doi/10.1126/science.adv2861