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

Abstract

Chromatin organization plays a key role in the regulation of gene expression^1,2. The evolutionarily conserved SWI/SNF complex is one of several multiprotein complexes that activate transcription by remodelling chromatin in an ATP-dependent manner^3,4,5. 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 proteins using the two-hybrid system^10,11 led to the isolation of c-MYC, a transactivator^12,13. 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.