Ensembl Regulation provides resources used for studying gene expression and its regulation in human and mouse, with a focus on the transcriptional and post-transcriptional mechanisms. The database includes the Ensembl Regulatory Build, an up-to-date and comprehensive summary of regulatory features across the genome, as well as popular curated external resources.

Accessing Ensembl regulation data

Regulation data in Ensembl can also be accessed through:

• The Browser

• BioMart (Ensembl Regulation database)

• Perl APIs, including the Regulation API

Browser access

Regulation data can be accessed in the browser from many angles:

Location Tab

We can configure the Region in detail panel to display tracks linked to regulation. The Regulation tracks are grouped into subdivisions:

• Regulatory Features: these can be visualized using the 'Regulatory Build' track.

• Activity Levels: select the cell type/line of interest and display the activity levels for each regulatory feature defined in the Regulatory Build.

• Segmentation Features: select the cell type/line of interest and display the genomic state assignment in the region.

• Open Chromatin and Transcription Factor Binding Sites (TFBS): display of signal or peaks from assays measuring open chromatin (DNAse-seq) or transcription factor binding (ChIP-seq) in many cell types/lines.

• Histones and Polymerases: display of signal or peaks from experimental ChIP-seq assays measuring histone marks/modifications or binding of RNA Polymerases II and III.

• DNA Methylation: RRBS and WGBS methylation tracks.

• Other regulatory regions: imported tracks from external databases.

Species-specific microarray probe mappings can be visualized by turning on tracks from the separate 'Oligo probes' section at the bottom of the configuration panel.

Gene tab

Click on the Regulation link in the left hand side menu to view the regulatory features and GTEx SNP-gene associations in the vicinity of our gene.

Regulation tab

Clicking on a regulatory feature will open a Regulation tab with information about the evidence supporting that regulatory feature as well as cell-specific activity estimates. Different views can be selected:

• Summary: this view displays the selected regulatory feature from the Regulatory Build. No cell-type specific activity levels are displayed by default.

• Details by cell type: this view displays the activity of the regulatory feature in any selected cell type (HUVEC by default) along with a default set of supporting evidence.

• Feature Context: this view displays the regulatory features in a wider context around the chosen regulatory feature and their activity levels across all available cell types.

• Evidence: this view displays the complete list of supporting core evidence, such as histone modifications presence, transcription factor binding and open chromatin, for the chosen regulatory feature in a table.

Regulatory features

Regions that are predicted to regulate gene expression are called Regulatory features in Ensembl. The different types of regulatory features annotated include:

• Promoters (regions at the 5' end of genes where transcription factors and RNA polymerase bind to initiate transcription)

• Promoter flanking regions (transcription factor binding regions that flank the above)

• Enhancers (regions that bind transcription factors and interact with promoters to stimulate transcription of distant genes)

• CTCF binding sites (regions that bind CTCF, the insulator protein that demarcates open and closed chromatin)

• Transcription factor binding sites (sites which bind transcription factors, for which no other role can be determined as yet)

• Open chromatin regions (regions of spaced out histones, making them accessible to protein interactions)

For each cell type the regulatory features are assigned labels to describe their activity levels. These include:

• ACTIVE, when the feature displays an active epigenetic signature.

• POISED, when the feature displays a epigenetic signature with the potential to be activated.

• REPRESSED, when the feature is epigenetically repressed.

• INACTIVE, when the region bears no epigenetic modifications from the ones included in the Regulatory Build.

• NA, when there is no available data in the cell type for this feature.

Determination of regulatory features

Regulatory features are inferred from publicly available experimental data sets, including:

• Open chromatin assays (DNase-seq)

• Histone modification assays (ChIP-seq)

• Transcription factor binding assays (ChIP-seq)