Chromatin organization plays a key role in the regulation of gene expressio
n(1,2). The evolutionarily conserved SWI/SNF complex is one of several mult
iprotein complexes that activate transcription by remodelling chromatin in
an ATP-dependent manner(3-5). SWI2/SNF2 is an ATPase whose homologues, BRG1
and hBRM, mediate cell-cycle arrest(6,7); the SNF5 homologue, INI1/hSNF5,
appears to be a tumour suppressor(8,9). A search for INI1-interacting prote
ins using the two-hybrid system(10,11) led to the isolation of c-MYC, a tra
nsactivator(12,13). The c-MYC-INI1 interaction was observed both in vitro a
nd 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 intera
ction. c-MYC-mediated transactivation was inhibited by a deletion fragment
of INI1 and the ATPase mutant of BRG1/hSNF2 in a dominant-negative manner c
ontingent upon the presence of the c-MYC bHLH-Zip domain. Our results sugge
st that the SWI/SNF complex is necessary for c-MYC-mediated transactivation
and that the c-MYC-INI1 interaction helps recruit the complex.