Description

The ENCODE project has established an epigenomic resource for mammalian development, profiling a diverse panel of mouse tissues at eight developmental stages from 10.5 days post conception until birth.

This track set presents enhancer-promoter interactions predicted from correlation of enhancer-associated chromatin signals and gene expression across tissue stages, based on histone modification (ChIP-seq) and transcription (RNA-seq) assays and analysis performed by the ENCODE project.

Data underlying this track are presented in the Histone Modifications and Chromatin State tracks, part of the ENCODE Regulation supertrack.

The promoters presented in this track were derived from experimentally validated promoters provided by the Eukaryotic Promoter Database (EPDNew). A more complete presentation of this annotation can be found in the EPDnew Promoters track.

Display Conventions and Configuration

This track is a multi-view composite track containing four data types (views):

• Putative enhancer elements
• Gene promoters
• Predicted interactions between enhancers and gene
• Clustered interactions, by gene or enhancer

For each view, there is a choice of two subtracks to display individually on the browser; the full set of interactions (and component promoters and enhancers), and a more stringent set, containing only interactions replicated in two biological replicates. Instructions for configuring multi-view tracks are here.

The display aims to improve distinguishing genes and their interactions by coloring successive genes in different colors. All interactions with a gene are colored the same as the gene promoter.

The promoter display follows EPD conventions; the "thin" part of the item represents the 49 bp upstream of the annotated transcription start site (TSS) whereas the "thick" part represents the TSS plus 10 bp downstream. The relative position of the thick and thin parts define the orientation of the promoter.

Methods

Enhancers

Strong enhancer calls from ChromHMM were merged and filtered to produce a set of 66,556 putative strong TSS-distal enhancers across all tissues and developmental stages, and H3K27ac signals at these regions were quantified using uniquely aligned, de-duplicated ChIP-seq reads.

Enhancer/Gene Map

Topologically associated domains (TAD's) identified in mouse ES-cells (Dixon et al.) were then used to constrain enhancer/gene associations. All protein-coding genes and putative strong enhancers within each TAD were evaluated in terms of the Spearman's correlation (SCC) between the H3K27ac pattern of enrichment and the mRNA expression from RNA-seq across samples. The SCC of each enhancer was calculated with reference to all genes on the chromosome, and this metric was used to estimate p-value by two strategies. Putative enhancers showing a p-value <= 0.05 (from both strategies)and a SCC >= 0.25 were retained.

Two maps were independently derived from two biological replicates of ChIP-seq and RNA-seq data. The "All" dataset contains significant interactions present in either biological replicate. The "Replicated" dataset contains significant interactions present in both Detailed methods can be found in Gorkin et al, in References below.

Promoters and Interactions

The Promoter subtrack was generated at UCSC. EPDnew mouse promoter release 003 (June 2018) was obtained from obtained from the Eukaryotic Promoter Database, and filtered to contain only promoters appearing in the Enhancer/Gene maps.

The Interactions view was generated at UCSC from the Enhancer/Gene maps by linking the enhancers to promoter regions based on the EPDnew promoters. Multiple promoters for a single gene were merged into a single region covering the range of all promoters.

Data Access

Histone ChIP-seq and RNA-seq data underlying this annotation are available from the ENCODE portal.

The EPDnew promoters for mouse can be downloaded from the EPD FTP site.

Credits

Thanks to Iros Barozzi and colleagues in the Environmental Genomics and Systems Biology Division at the Lawrence Berkeley National Laboratory for generating the enhancer/gene association analysis and to David Gorkin and Yanxiao Zhang at the Ren lab (UCSD/Ludwig Institute for Cancer Research) for providing these data and assisting with track development at UCSC.

References

Gorkin et al. An atlas of dynamic chromatin landscapes in the developing mouse fetus. Nature, In Press. (pre-print: doi: https://doi.org/10.1101/166652)

Dreos R, Ambrosini G, Groux R, Cavin Périer R, Bucher P. The eukaryotic promoter database in its 30th year: focus on non-vertebrate organisms. Nucleic Acids Res. 2017 Jan 4;45(D1):D51-D55. PMID: 27899657; PMC: PMC5210552

Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012 Apr 11;485(7398):376-80. PMID: 22495300; PMC: PMC3356448