Ensembl Regulation

Description

The Ensembl Regulation team is part of the broader Ensembl project. We develop, adapt and run computational methods to identify and characterise genomic regulatory elements, such as promoters, enhancers and CTCF binding sites.

Our work focuses on species of key importance to biomedical and agricultural research. We currently provide regulatory annotation for human and mouse, and major livestock and aquaculture species.

Our annotations are based primarily on ChIP-seq, DNase-seq, and ATAC-seq data generated by the ENCODE and FAANG consortia, and gene annotation from Ensembl/GENCODE.

Display conventions and configuration

Regulatory features are coloured by feature type. The colours below are the values stored in the data files, so they match what is drawn in the browser image:

Each feature links back to its Ensembl Regulation page. The feature type is shown on hover and on the details page reached by clicking a feature.

Available assemblies

An Ensembl Regulation release includes the latest version of annotation for each assembly available at the time of the release, although annotation is not necessarily updated for every species in every release. The Last updated column in the table below indicates the annotation date for each assembly in this release. The corresponding annotation and regulatory feature details can be found at the Ensembl Regulation site (https://regulation.ensembl.org) using any release from that update until the annotation is next updated.

UCSC genome releases

Genome Archive species (GenArk)

Methods

Ensembl's regulatory features are based on open chromatin regions. The first step is primary analysis, where sequencing reads from genomic assays such as ChIP-seq and ATAC-seq are mapped to the genome and enriched regions (peaks) are identified. The results of primary analysis are then used to produce the final annotation of regulatory features.

Open chromatin union peaks (OCUPs)

We first produce a set of open chromatin union peaks (OCUPs), which are a union of ATAC-seq and DNase-seq peaks present across sufficient epigenomes for the given species.

Promoters

Promoters are OCUPs that overlap transcription start sites (-90 to +10 bp). We define transcription start sites (TSSs) as the 5' end of protein-coding or lncRNA transcripts, excluding those annotated as having an unknown 5' end (relevant for GENCODE annotation). We further refine the promoter annotation by defining a promoter core region using larger TSS windows (-490 to +10 bp) and merging overlapping regions. We then calculate the promoter's extended region based on the OCUP, but limited upstream by 1 kb and downstream to +10 bp of the furthest TSS.

Enhancers and open chromatin regions

For the remaining OCUPs, we:

• Merge those that are within 100 bp (excluding promoters) and discard those < 100 bp.
• Merge H3K4me1, H3K27ac and open chromatin peaks within 100 bp across epigenomes into merged union peaks (MUPs). Discard histone MUPs that do not overlap the open chromatin MUPs by at least 50% in either direction.
• OCUPs larger than 2.5 kb are trimmed by intersecting with H3K27ac MUPs if possible, or discarded.
• OCUPs overlapping H3K4me1 or H3K27ac MUPs by more than 50% are labelled as enhancers, unless they overlap coding sequence by more than 10%, in which case they are discarded.
• The remaining OCUPs are classified as open chromatin regions.

Data access

The underlying bigBed files can be downloaded from the table above, or queried directly with the UCSC Table Browser and the command line utilities bigBedInfo, bigBedToBed and bigBedSummary, available from our downloads server. GFF versions of the same annotation are also linked above.

Further documentation from Ensembl Regulation:

• Primary processing
• Regulatory build
• Source data
• Epigenomes

Contact

If you have questions or suggestions about this annotation, please contact the Ensembl Regulation team at helpdesk@ensembl.org.

Credits

The regulatory annotation is produced and hosted by the Ensembl Regulation team at the European Bioinformatics Institute (EMBL-EBI).

References

Ilsley GR, Branco Lins PR, Merino GA, Urbina-Gomez D, Harrison PW. Ensembl's regulatory annotation for human, mouse, livestock, and aquaculture species. Preprint, 2026. https://doi.org/10.21203/rs.3.rs-8007521/v1