BRG1 contributes to the global chromatin accessibility revealed by its acute depletion

DNase I hypersensitivity (DHS) of chromatin indicates the presence of important regulatory elements of transcription such as enhancers and promoters and plays critical roles for their activities. However, the mechanisms that control the global DHS have not been fully understood. In this report, we show that acute depletion of BRG1 by the auxin-dependent degron system, the essential ATPase subunit of the mammalian chromatin remodeling SWI/SNF-like BAF complexes, severely compromised genome-wide DHSs of chromatin, while the traditional conditional deletion of the Brg1 gene using Cre/Flox system led to only very modest changes of DHSs. The global decrease of DHSs is associated with a genome-wide decrease of transcription. We demonstrate that the DHS change is related with changes in nucleosome positioning at promoters and enhancers. Our data suggest that acute depletion of proteins reveal target genes of BRG1 that are not detected by the traditional models. To address the direct effect of BRG1 depletion in gene regulation and chromatin landscape, we employ auxin-dependent degron (AID) system to acute deplete BRG1 in mouse T cells and hepatocytes. We further validated these directly effects by comparison with the traditional conditional deletion of the Brg1 gene using Cre/Flox system. Integration analysis of multi-omics datasets, we uncover the novel mechanism for BRG1 dependent regulation of gene expression and chromatin landscape, which are not detected by the traditional models.