| First Author | Kim B | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 2 | Pages | 109357 |
| PubMed ID | 34260936 | Mgi Jnum | J:321420 |
| Mgi Id | MGI:6874575 | Doi | 10.1016/j.celrep.2021.109357 |
| Citation | Kim B, et al. (2021) Neuronal activity-induced BRG1 phosphorylation regulates enhancer activation. Cell Rep 36(2):109357 |
| abstractText | Neuronal activity-induced enhancers drive gene activation. We demonstrate that BRG1, the core subunit of SWI/SNF-like BAF ATP-dependent chromatin remodeling complexes, regulates neuronal activity-induced enhancers. Upon stimulation, BRG1 is recruited to enhancers in an H3K27Ac-dependent manner. BRG1 regulates enhancer basal activities and inducibility by affecting cohesin binding, enhancer-promoter looping, RNA polymerase II recruitment, and enhancer RNA expression. We identify a serine phosphorylation site in BRG1 that is induced by neuronal stimulations and is sensitive to CaMKII inhibition. BRG1 phosphorylation affects its interaction with several transcription co-factors, including the NuRD repressor complex and cohesin, possibly modulating BRG1-mediated transcription outcomes. Using mice with knockin mutations, we show that non-phosphorylatable BRG1 fails to efficiently induce activity-dependent genes, whereas phosphomimic BRG1 increases enhancer activity and inducibility. These mutant mice display anxiety-like phenotypes and altered responses to stress. Therefore, we reveal a mechanism connecting neuronal signaling to enhancer activities through BRG1 phosphorylation. |
