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

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 associates with eRNA 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: Immunoprecipitated samples (Brg1, H3K27ac, Med1, H3K4me1 and MLL3/4) and mock control samples (IgG) were prepared for biological duplicates of wild type (WT) and two AT hook domain deletion mutants (dAT1, dAT2) in naïve and primed conditions. These samples were sequenced by 75bp paired-end, Illumina HiSeq3000.