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

• Published in: Nature genetics Vol. 22; no. 1; pp. 102 - 105
• Main Authors: Kalpana, Ganjam V, Cheng, S.-W. Grace, Davies, Kelvin P, Yung, Eric, Beltran, Ralph J, Yu, Jin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.05.1999
• Subjects: Binding Sites; Biological and medical sciences; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosomal Proteins, Non-Histone; DNA Helicases; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila Proteins; Fundamental and applied biological sciences. Psychology; HeLa Cells; HL-60 Cells; Humans; Molecular and cellular biology; 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; Ribonucleoprotein, U1 Small Nuclear - metabolism; RNA-Binding Proteins; SMARCB1 Protein; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation; Molecular arrangement; Human; Chromatin; Regulation(control); Cell line; Gene; C-Onc gene; Molecular interaction; Binding site; Transcription factor; Gene expression
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/8811

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.