Super-enhancer switching in early mammalian development involves eRNA mediated SWI/SNF recruitment [RIP-seq]

The RNA transcribed from enhancer regions, referred to as eRNA, has been suggested to directly activate transcription by helping to recruit transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find the AT-hook of SWI/SNF alone binds preferentially RNA and as part of the esBAF complexes likely associates with eRNA that are transcribed from intronic and intergenic regions. SWI/SNF is globally recruited in cis by eRNA to cell-type specific enhancers at two distinct stages in early mammalian development and not at promoters or enhancers that are shared between the two stages. SWI/SNF recruited by eRNA facilitates recruitment and/or activation of MLL3/4, p300/CBP and Mediator co-activators to stage-specific super-enhancers that in the primed embryonic stage activate cell lineage priming related genes. We find a strong connection between ATP-dependent chromatin remodeling and eRNA in cell identity and super-enhancer activation. Overall design: To investigate the RNA binding affinity of Brg1 and its AT hook domain and the characteristics of Brg1 bound RNAs, we first created Brg1 HA tagged and AT hook domain knock-out E14 cell lines. After then, we identified AT hook domain dependently Brg1 binding RNAs using RIP-seq data.