c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function

Nat Genet. 1999 May;22(1):102-5. doi: 10.1038/8811.

Abstract

Chromatin organization plays a key role in the regulation of gene expression. The evolutionarily conserved SWI/SNF complex is one of several multiprotein complexes that activate transcription by remodelling chromatin in an ATP-dependent manner. SWI2/SNF2 is an ATPase whose homologues, BRG1 and hBRM, mediate cell-cycle arrest; the SNF5 homologue, INI1/hSNF5, appears to be a tumour suppressor. A search for INI1-interacting proteins using the two-hybrid system led to the isolation of c-MYC, a transactivator. The c-MYC-INI1 interaction was observed both in vitro and in vivo. The c-MYC basic helix-loop-helix (bHLH) and leucine zipper (Zip) domains and the INI1 repeat 1 (Rpt1) region were required for this interaction. c-MYC-mediated transactivation was inhibited by a deletion fragment of INI1 and the ATPase mutant of BRG1/hSNF2 in a dominant-negative manner contingent upon the presence of the c-MYC bHLH-Zip domain. Our results suggest that the SWI/SNF complex is necessary for c-MYC-mediated transactivation and that the c-MYC-INI1 interaction helps recruit the complex.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Line
  • Chromosomal Proteins, Non-Histone
  • DNA Helicases
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins*
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA-Binding Proteins*
  • Ribonucleoprotein, U1 Small Nuclear / metabolism*
  • SMARCB1 Protein
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA-Binding Proteins
  • Ribonucleoprotein, U1 Small Nuclear
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • snf protein, Drosophila
  • SMARCA4 protein, human
  • DNA Helicases