| Title: |
An expanded registry of candidate cis-regulatory elements |
| Authors: |
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; Guigó, 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 |
| Contributors: |
Genomics and Computational Biology |
| Source: |
Nature ; England |
| Publication Year: |
2026 |
| Collection: |
University of Massachusetts, Medical School: eScholarship@UMMS |
| Description: |
Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. 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 functions. 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-seq, massively parallel reporter assay, CRISPR perturbation and transgenic mouse assays 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. ; No embargo |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
This article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2024.12.26.629296.; Nature; https://doi.org/10.1038/s41586-025-09909-9; https://hdl.handle.net/20.500.14038/55068 |
| DOI: |
10.1038/s41586-025-09909-9 |
| Availability: |
https://doi.org/10.1038/s41586-025-09909-9; https://hdl.handle.net/20.500.14038/55068 |
| Rights: |
Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2026 ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.61398A7D |
| Database: |
BASE |