A Muscle-Specific Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription in Trans

The enhancer regions of the myogenic master regulator MyoD give rise to at least two enhancer RNAs. CEeRNA regulates transcription of the adjacent MyoD gene while DRReRNA affects expression of Myogenin in trans. We found that DRReRNA is recruited at the Myogenin locus where it colocalizes with Myogenin nascent transcripts. DRReRNA associates with the Cohesin complex and such association correlates with its transactivating properties. Despite being expressed in undifferentiated cells, Cohesin is not loaded on Myogenin until the cells start expressing DRReRNA, which is then required for Cohesin chromatin recruitment and maintenance. Functionally, depletion of either Cohesin or DRReRNA reduces chromatin accessibility, prevents Myogenin activation, and hinders muscle cell differentiation. Thus, DRReRNA ensures spatially appropriate Cohesin loading in trans to regulate gene expression. Examination of genome-wide distribution of DRReRNA, SMC3 and chromatin accessibility in mouse C2C12 myoblast cells.