An expanded registry of candidate cis-regulatory elements.

Area of Science:

• Genomics
• Regulatory Biology
• Bioinformatics

Background:

• Mammalian genomes possess millions of regulatory elements controlling gene expression.
• The ENCODE consortium previously cataloged 0.9 million human and 300,000 mouse candidate cis-regulatory elements (cCREs).

Purpose of the Study:

• To expand the ENCODE registry of cCREs using new datasets and computational methods.
• To provide a comprehensive resource for understanding gene regulation across diverse cell and tissue types.

Main Methods:

• Leveraged new ENCODE datasets and enhanced computational approaches.
• Integrated functional characterization data from assays like STARR-seq, MPRA, CRISPR, and transgenic mouse models.
• Expanded the registry to include 2.37 million human and 967,000 mouse cCREs.

Main Results:

• The expanded registry covers hundreds of cell and tissue types, enhancing understanding of gene regulation.
• Over 90% of human cCREs were functionally profiled, revealing complex regulatory roles.
• Thousands of novel silencer cCREs were identified, some exhibiting dual enhancer/silencer functions.
• KLF1 was identified as a novel causal gene for red blood cell traits.

Conclusions:

• The expanded ENCODE cCRE registry is a valuable resource for regulatory genomics research.
• Integration with other ENCODE data aids in interpreting genetic variation and identifying trait-associated genes.
• This resource advances the study of the regulatory genome's role in health and disease.