Super-enhancer Dynamics Throughout Myogenesis

Genome-wide ChIP-seq analysis of transcription factor binding and histone marks has uncovered large regulatory domains, known as super-enhancers, that consist of clusters of active enhancers within 12.5 kb of each other. Super-enhancers are characterized by high abundance of H3K27ac histone marks, disproportionate binding of master regulators and coactivators, and drive the expression of important cell identity genes. The algorithm, Rank Ordering of Super-Enhancers (ROSE), was developed to identify SEs based on their characteristics and has been extensively used, on various cell types. Less attention has been aimed at understanding how super-enhancers change in different cellular contexts, and in particular, during the differentiation of stem cells. We use ROSE, in conjunction with other tools, to investigate the dynamics of super-enhancers across myogenesis. Using ChIP-seq data for various transcription factors and stage-matched RNA-seq data, we characterize several super-enhancer regions and their associated genes in myoblasts and myotubes, finding them to be largely stage-specific.