Investigating the role of super-enhancer RNAs underlying embryonic stem cell differentiation

Abstract

Background: Super-enhancer RNAs (seRNAs) are a kind of noncoding RNA transcribed from super-enhancer regions. The regulation mechanism and functional role of seRNAs are still unclear. Although super-enhancers play a critical role in the core transcriptional regulatory circuity of embryonic stem cell (ESC) differentiation, whether seRNAs have similar properties should be further investigated. Results: We analyzed cap analysis gene expression sequencing (CAGE-seq) datasets collected during the differentiation of embryonic stem cells (ESCs) to cardiomyocytes to identify the seRNAs. A non-negative matrix factorization algorithm was applied to decompose the seRNA profiles and reveal two hidden stages during the ESC differentiation. We further identified 95 and 78 seRNAs associated with early- and late-stage ESC differentiation, respectively. We found that the binding sites of master regulators of ESC differentiation, including NANOG, FOXA2, and MYC, were significantly observed in the loci of the stage-specific seRNAs. Based on the investigation of genes coexpressed with seRNA, these stage-specific seRNAs might be involved in cardiac-related functions such as myofibril assembly and heart development and act in trans to regulate the co-expressed genes. Conclusions: In this study, we used a computational approach to demonstrate the possible role of seRNAs during ESC differentiation.