Neuronal activity-induced BRG1 phosphorylation regulates enhancer activation

Bong Woo Kim, Yi Luo, Xiaoming Zhan, Zilai Zhang, Xuanming Shi, Jiaqing Yi, Zhenyu Xuan, Jiang Wu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number109357
JournalCell Reports
Volume36
Issue number2
DOIs
StatePublished - Jul 13 2021

Keywords

  • BRG1/SMARCA4
  • CaMKII
  • NuRD
  • PFI-3
  • chromatin remodeling
  • enhancer
  • enhancer-promoter looping
  • immediate early genes
  • neuronal activity-regulated genes
  • phosphorylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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