Activity-assembled nBAF complex mediates rapid immediate early gene transcription by regulating RNA polymerase II productive elongation

SUMMARY Signal-dependent RNA polymerase II (RNA Pol II) productive elongation is an integral component of gene transcription, including that of immediate early genes (IEGs) induced by neuronal activity. However, it remains unclear how productively elongating RNA Pol II overcomes nucleosomal barriers. Using RNAi, three degraders, and several small-molecule inhibitors, we show that the mammalian switch/sucrose non-fermentable (SWI/SNF) complex of neurons (neuronal BRG1/BRM-associated factor or nBAF) is required for activity-induced transcription of neuronal IEGs, including Arc. The nBAF complex facilitates promoter-proximal RNA Pol II pausing and signal-dependent RNA Pol II recruitment (loading) and, importantly, mediates productive elongation in the gene body via interaction with the elongation complex and elongation-competent RNA Pol II. Mechanistically, RNA Pol II elongation is mediated by activity-induced nBAF assembly (especially ARID1A recruitment) and its ATPase activity. Together, our data demonstrate that the nBAF complex regulates several aspects of RNA Pol II transcription and reveal mechanisms underlying activity-induced RNA Pol II elongation. These findings may offer insights into human maladies etiologically associated with mutational interdiction of BAF functions.

• Publication year

  2024

• Venue

  Cell Reports

• Publication date

  2024-10-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.celrep.2024.114877PMID 39412992PMCID 11625021
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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