biostudies-literatureHagihara YNICHD NIH HHSU.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)2250-2263https://www.ebi.ac.uk/biostudies/studies/S-EPMC12425804biostudies-literatureUnknown57(9)Mammalian switch/sucrose nonfermentable (mSWI/SNF) complex regulates chromatin accessibility and frequently shows alterations due to mutation in cancer and neurological diseases. Inadequate expression of mSWI/SNF in heterozygous mice can lead to developmental defects, indicating dosage-sensitive effects of mSWI/SNF. However, how its dosage affects function has remained unclear. Using a targeted protein degradation system, we investigated its dosage-sensitive effects by precisely controlling protein levels of BRG1, the ATPase subunit of the mSWI/SNF complex. We found that binding of BRG1 to chromatin exhibited a linear response to the BRG1 protein level. Although chromatin accessibility at most promoters and insulators was largely unaffected by BRG1 depletion, 44% of enhancers, including 84Nature geneticsPrecise modulation of BRG1 levels reveals features of mSWI/SNF dosage sensitivity.PMC12425804R01HD092465R01 HD092465Zhang YZhang CHagihara YfalsePrecise modulation of BRG1 levels reveals features of mSWI/SNF dosage sensitivity.Mammalian switch/sucrose nonfermentable (mSWI/SNF) complex regulates chromatin accessibility and frequently shows alterations due to mutation in cancer and neurological diseases. Inadequate expression of mSWI/SNF in heterozygous mice can lead to developmental defects, indicating dosage-sensitive effects of mSWI/SNF. However, how its dosage affects function has remained unclear. Using a targeted protein degradation system, we investigated its dosage-sensitive effects by precisely controlling protein levels of BRG1, the ATPase subunit of the mSWI/SNF complex. We found that binding of BRG1 to chromatin exhibited a linear response to the BRG1 protein level. Although chromatin accessibility at most promoters and insulators was largely unaffected by BRG1 depletion, 44% of enhancers, including 842025-01-01T00:00:00Z2025 Sep2026-06-01T12:05:37.749Z2026-04-08T12:03:01.817ZS-EPMC124258044084676310.1038/s41588-025-02305-z