The SWI/SNF Subunit INI1 Contains an N-Terminal Winged Helix DNA Binding Domain that Is a Target for Mutations in Schwannomatosis

Structure. 2015 Jul 7;23(7):1344-9. doi: 10.1016/j.str.2015.04.021. Epub 2015 Jun 11.

Abstract

SWI/SNF complexes use the energy of ATP hydrolysis to remodel chromatin. In mammals they play a central role in regulating gene expression during differentiation and proliferation. Mutations in SWI/SNF subunits are among the most frequent gene alterations in cancer. The INI1/hSNF5/SMARCB1 subunit is mutated in both malignant rhabdoid tumor, a highly aggressive childhood cancer, and schwannomatosis, a tumor-predisposing syndrome characterized by mostly benign tumors of the CNS. Here, we show that mutations in INI1 that cause schwannomatosis target a hitherto unidentified N-terminal winged helix DNA binding domain that is also present in the BAF45a/PHF10 subunit of the SWI/SNF complex. The domain is structurally related to the SKI/SNO/DAC domain, which is found in a number of metazoan chromatin-associated proteins.

MeSH terms

  • Amino Acid Sequence
  • Chromosomal Proteins, Non-Histone / genetics*
  • Conserved Sequence
  • DNA-Binding Proteins / genetics*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Neurilemmoma / genetics*
  • Neurofibromatoses / genetics*
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • SMARCB1 Protein
  • Skin Neoplasms / genetics*
  • Transcription Factors / genetics*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors

Supplementary concepts

  • Schwannomatosis