马萨诸塞州大学医学院翁志萍小组近日取得一项新成果。经过不懈努力，他们研制了候选顺式调控元件扩展注册表。相关论文发表在2026年1月7日出版的《自然》杂志上。

在这里，该课题组利用新的ENCODE数据集和增强的计算方法，将注册表扩展到包括237万个人类和96.7万个非主题cCREs。这个扩展的注册表涵盖了数百种独特的细胞和组织类型，提供了对基因调控的全面了解。来自诸如STARR-seq、大规模平行报告基因分析、CRISPR微扰和转基因小鼠分析等分析的功能表征数据已经分析了超过90%的人类cCREs，揭示了复杂的调控功能。课题组人员确定了新型消音器cCREs的需求，并证明了它们在不同细胞环境中的双重增强和消音器作用。将注册表与其他ENCODE注释相结合，有助于遗传变异解释和性状相关基因鉴定，例如鉴定出KLF1是一种新的红细胞性状诱导基因。这种扩展的登记是研究调控基因组及其对健康和疾病影响的宝贵阻力。

研究人员表示，哺乳动物基因组包含数以百万计的调控元件，它们控制着复杂的基因表达模式。此前，ENCODE联盟绘制了数百种细胞类型和组织的生化信号，并整合了这些数据，建立了一个包含90万个人类和30万个具有潜在功能的小鼠候选顺式调控元件（cCREs）的注册表。

附：英文原文

Title: An expanded registry of candidate cis-regulatory elements

Author: Moore, Jill E., Pratt, Henry E., Fan, Kaili, Phalke, Nishigandha, Fisher, Jonathan, Elhajjajy, Shaimae I., Andrews, Gregory, Gao, Mingshi, Shedd, Nicole, Fu, Yu, Lacadie, Matthew C., Meza, Jair, Khandpekar, Mansi, Ganna, Mohit, Choudhury, Eva, Swofford, Ross, Phan, Huong, Ramirez, Christian C., Campbell, Maxwell, Likhite, Mary, Farrell, Nina P., Weimer, Annika K., Pampari, Anusri, Ramalingam, Vivekanandan, Reese, Fairlie, Borsari, Beatrice, Yu, Xuezhu, Wattenberg, Eve, Ruiz-Romero, Marina, Razavi-Mohseni, Milad, Xu, Jinrui, Galeev, Timur, Colubri, Andres, Beer, Michael A., Guig, Roderic, Gerstein, Mark B., Engreitz, Jesse M., Ljungman, Mats, Reddy, Timothy E., Snyder, Michael P., Epstein, Charles B., Gaskell, Elizabeth, Bernstein, Bradley E., Dickel, Diane E., Visel, Axel, Pennacchio, Len A., Mortazavi, Ali, Kundaje, Anshul, Weng, Zhiping

Issue&Volume: 2026-01-07

Abstract: Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression1. Previously, the ENCODE consortium mapped biochemical signals across hundreds of cell types and tissues and integrated these data to develop a registry containing 0.9 million human and 300,000 mouse candidate cis-regulatory elements (cCREs) annotated with potential functions2. Here we have expanded the registry to include 2.37 million human and 967,000 mouse cCREs, leveraging new ENCODE datasets and enhanced computational methods. This expanded registry covers hundreds of unique cell and tissue types, providing a comprehensive understanding of gene regulation. Functional characterization data from assays such as STARR-seq3, massively parallel reporter assay4, CRISPR perturbation5,6 and transgenic mouse assays7 have profiled more than 90% of human cCREs, revealing complex regulatory functions. We identified thousands of novel silencer cCREs and demonstrated their dual enhancer and silencer roles in different cellular contexts. Integrating the registry with other ENCODE annotations facilitates genetic variation interpretation and trait-associated gene identification, exemplified by the identification of KLF1 as a novel causal gene for red blood cell traits. This expanded registry is a valuable resource for studying the regulatory genome and its impact on health and disease.

DOI: 10.1038/s41586-025-09909-9

Source: https://www.nature.com/articles/s41586-025-09909-9