Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF

Approximately 75% of the human genome is transcribed, the majority of which does not encode protein. However, most noncoding RNA (ncRNA) is rapidly degraded after transcription, and relatively few have established functions, questioning the significance of this observation. Here we show that esBAF, a SWI/SNF family nucleosome remodeling factor, suppresses transcription of ncRNAs from approximately 57,000 nucleosome-depleted regions (NDRs) throughout the genome of mouse embryonic stem cells (ESCs). We show that esBAF functions both to keep NDRs nucleosome-free and to promote elevated nucleosome occupancy adjacent to NDRs. Reduction of adjacent nucleosome occupancy upon esBAF depletion is strongly correlated with ncRNA expression, suggesting that flanking nucleosomes form a barrier to pervasive transcription. Upon forcing nucleosome occupancy near an NDR using a nucleosome-positioning sequence, we find that esBAF is no longer required to silence transcription. These data reveal a novel role for esBAF in suppressing pervasive transcription from open chromatin regions in ESCs. Overall design: Examine nucleosome occupancy (MNase-Seq) and transcript production (CapSeq and RNA-Seq) in EGFP KD and Smarca4 KD ESCs

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Hainer SJ, Gu W, Carone BR, Landry BD, Rando OJ, Mello CC, Fazzio TG