TY - JOUR T1 - Enhancer RNAs predict enhancer-gene regulatory links and are critical for enhancer function in neuronal systems JF - bioRxiv DO - 10.1101/270967 SP - 270967 AU - Nancy V. N. Carullo AU - Robert A. Phillips III AU - Rhiana C. Simon AU - Salomon A. Roman Soto AU - Jenna E. Hinds AU - Aaron J. Salisbury AU - Jasmin S. Revanna AU - Kendra D. Bunner AU - Lara Ianov AU - Faraz A. Sultan AU - Katherine E. Savell AU - Charles A. Gersbach AU - Jeremy J. Day Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/16/270967.abstract N2 - Genomic enhancer elements regulate gene expression programs important for neuronal fate and function and are implicated in brain disease states. Enhancers undergo bidirectional transcription to generate non-coding enhancer RNAs (eRNAs). However, eRNA function remains controversial. Here, we combined ATAC-Seq and RNA-Seq datasets from three distinct neuronal culture systems in two activity states, enabling genome-wide enhancer identification and prediction of putative enhancer-gene pairs based on correlation of transcriptional output. Notably, stimulus-dependent enhancer transcription preceded mRNA induction, and CRISPR- based activation of eRNA synthesis increased mRNA at paired genes, functionally validating enhancer-gene predictions. Focusing on enhancers surrounding the Fos gene, we report that targeted eRNA manipulation bidirectionally modulates Fos mRNA, and that Fos eRNAs directly interact with the histone acetyltransferase domain of the enhancer-linked transcriptional co-activator CBP. Together, these results highlight the unique role of eRNAs in neuronal gene regulation and demonstrate that eRNAs can be used to identify putative target genes.Competing Interest StatementThe authors have declared no competing interest. ER -