An expanded registry of candidate cis-regulatory elements
Abstract
Abstract Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression 1 . 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 2 . 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 3 , massively parallel reporter assay 4 , CRISPR perturbation 5,6 and transgenic mouse assays 7 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.
Article Details
Authors (49)
Jill E. Moore
Henry E. Pratt
Kaili Fan
Nishigandha Phalke
Jonathan Fisher
Shaimae I. Elhajjajy
Gregory Andrews
Mingshi Gao
Nicole Shedd
Yu Fu
Matthew C. Lacadie
Jair Meza
Mansi Khandpekar
Mohit Ganna
Eva Choudhury
Ross Swofford
Huong Phan
Christian C. Ramirez
Maxwell Campbell
Mary Likhite
Nina P. Farrell
Annika K. Weimer
Anusri Pampari
Vivekanandan Ramalingam
Fairlie Reese
Beatrice Borsari
Xuezhu Yu
Eve Wattenberg
Marina Ruiz-Romero
Milad Razavi-Mohseni
Jinrui Xu
Timur Galeev
Andres Colubri
Michael A. Beer
Roderic Guigó
Mark B. Gerstein
Jesse M. Engreitz
Mats Ljungman
Timothy E. Reddy
Michael P. Snyder
Charles B. Epstein
Elizabeth Gaskell
Bradley E. Bernstein
Diane E. Dickel
Axel Visel
Len A. Pennacchio
Ali Mortazavi
Anshul Kundaje
Zhiping Weng