A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells

Nat Commun. 2018 Dec 3;9(1):5139. doi: 10.1038/s41467-018-07528-9.

Abstract

The role of individual subunits in the targeting and function of the mammalian BRG1-associated factors (BAF) complex in embryonic stem cell (ESC) pluripotency maintenance has not yet been elucidated. Here we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L) define a smaller, non-canonical BAF complex (GBAF complex) in mouse ESCs that is distinct from the canonical ESC BAF complex (esBAF). GBAF and esBAF complexes are targeted to different genomic features, with GBAF co-localizing with key regulators of naive pluripotency, which is consistent with its specific function in maintaining naive pluripotency gene expression. BRD9 interacts with BRD4 in a bromodomain-dependent fashion, which leads to the recruitment of GBAF complexes to chromatin, explaining the functional similarity between these epigenetic regulators. Together, our results highlight the biological importance of BAF complex heterogeneity in maintaining the transcriptional network of pluripotency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Mouse Embryonic Stem Cells / metabolism*
  • Pluripotent Stem Cells / metabolism*
  • RNA Interference
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors