Correlation Engine 2.0
Clear Search sequence regions

  • adipogenesis (1)
  • ATP (1)
  • BAF (8)
  • CEBPB (2)
  • chromatin (5)
  • DDIT3 (3)
  • human (1)
  • mammals (1)
  • myxoid liposarcoma (3)
  • oncoprotein (4)
  • SMARCB1 (1)
  • SNF (2)
  • stem cells (1)
  • subunit (1)
  • Sizes of these terms reflect their relevance to your search.

    Mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes play critical roles in governing genomic architecture and gene expression and are frequently perturbed in human cancers. Transcription factors (TFs), including fusion oncoproteins, can bind to BAF complex surfaces to direct chromatin targeting and accessibility, often activating oncogenic gene loci. Here, we demonstrate that the FUS::DDIT3 fusion oncoprotein hallmark to myxoid liposarcoma (MLPS) inhibits BAF complex-mediated remodeling of adipogenic enhancer sites via sequestration of the adipogenic TF, CEBPB, from the genome. In mesenchymal stem cells, small-molecule inhibition of BAF complex ATPase activity attenuates adipogenesis via failure of BAF-mediated DNA accessibility and gene activation at CEBPB target sites. BAF chromatin occupancy and gene expression profiles of FUS::DDIT3-expressing cell lines and primary tumors exhibit similarity to SMARCB1-deficient tumor types. These data present a mechanism by which a fusion oncoprotein generates a BAF complex loss-of-function phenotype, independent of deleterious subunit mutations. Copyright © 2022 Elsevier Inc. All rights reserved.


    Hayley J Zullow, Akshay Sankar, Davis R Ingram, Daniel D Samé Guerra, Andrew R D'Avino, Clayton K Collings, Rossana Lazcano, Wei-Lien Wang, Yu Liang, Jun Qi, Alexander J Lazar, Cigall Kadoch. The FUS::DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma. Molecular cell. 2022 May 05;82(9):1737-1750.e8

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 35390276

    View Full Text