Precise modulation of mSWI/SNF identified dosage-sensitive chromatin regulation [ATAC-Seq]

ATP-dependent chromatin remodelers establish and arrange nucleosome distribution, modifying accessibility of DNA. Brg1 is exclusive ATPase subunit of mSWI/SNF complex. To understand the dosage dependent function of mSWI/SNF complex. We take an advantage of dTag system to precisely control abundancy of BRG1. We found overall Brg1-binding is sensitive to its abundance nevertheless OCT4-target or H3K27ac region, suggesting Brg1 genome-wide distribution rather than being actively recruited. We also reveal open chromatin dependency on BRG1. The chromatin accessibility of super enhancer shows buffered response on depletion of BRG1, whereas weak enhancer is sensitive. Finally, transcriptomic analysis identified that transcription shows buffered dependencies on BRG1 loss. Overall, our results highlight kinetics differences of BRG1-binding to transcriptome underline BRG1 dosage-sensitive mechanism. Overall design: To study the kinetics of BRG1 binding, chromatin accessibility, and gene expression, we employed the dTAG system to precisely control Brg1 protein levels in mESCs. We then used Cut&Run, ATAC-seq, and RNA-seq to examine the kinetic changes under different Brg1 protein levels.