HeRA: an atlas of enhancer RNAs across human tissues

Abstract

Enhancer RNA (eRNA) is a type of long non-coding RNA transcribed from DNA enhancer regions. Despite critical roles of eRNA in gene regulation, the expression landscape of eRNAs in normal human tissue remains unexplored. Using numerous samples from the Genotype-Tissue Expression project, we characterized 45 411 detectable eRNAs and identified tens of thousands of associations between eRNAs and traits, including gender, race, and age. We constructed a co-expression network to identify millions of putative eRNA regulators and target genes across different tissues. We further constructed a user-friendly data portal, Human enhancer RNA Atlas (HeRA, https://hanlab.uth.edu/HeRA/). In HeRA, users can search, browse, and download the eRNA expression profile, trait-related eRNAs, and eRNA co-expression network by searching the eRNA ID, gene symbol, and genomic region in one or multiple tissues. HeRA is the first data portal to characterize eRNAs from 9577 samples across 54 human tissues and facilitates functional and mechanistic investigations of eRNAs.

Figure 1.

Computational framework for HeRA database. Blue blocks denote datasets used in this study. RNA-seq, traits and gene expression matrix were collected from GTEx. Enhancer annotation was collected from ENCODE, FANTOM and Roadmap Epigenetics Project. Transcription factors (TFs) were collected from AnimialTFDB, DBD, JASPAR and TF2DNA. Gene annotations were collected from ENSEMBL, GENCODE and UCSC. Red blocks denote processed data, including eRNA expression, traits, regulators and target genes. All processed data are available for downloading.

Figure 2.

Overview of HeRA database. (A) Four modules of HeRA: expression, traits, regulators, and targets. (B) Interface of search boxes for tissues in each module. Users can select one or more tissues for querying. Default is all tissues. (C) Interface of search boxes for eRNA in each module. Users may query through the genomic region, eRNA ID, or gene symbol. (D) Trait selection function in the traits module. Users can select one or more traits for querying. (E) Mean expression of ENSR00000282266 across tissues (bar) and in each individual sample of brain—cortex (dot). (F) Differential expression of ENSR00000246683 in lung tissue between females and males. (G) Significant correlation of ENSR00000191822 with age in splenic tissue. (H) Co-expression of ENSR00000189515 and putative regulator CTCF in brain—hippocampus. (I) Co-expression of ENSR00000341426 and putative target gene AR in prostate tissue.