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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 expression1,2. The evolutionarily conserved SWI/SNF complex is one of several multiprotein complexes that activate transcription by remodelling chromatin in an ATP-dependent manner3,4,5. SWI2/SNF2 is an ATPase whose homologues, BRG1 and hBRM, mediate cell-cycle arrest6,7; the SNF5 homologue, INI1/hSNF5, appears to be a tumour suppressor8,9. A search for INI1-interacting proteins using the two-hybrid system10,11 led to the isolation of c-MYC, a transactivator12,13. 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.

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Figure 1: INI1 interacts with c-MYC in the two-hybrid system.
Figure 2: INI1 directly interacts with c-MYC in vitro.
Figure 3: Co-immunoprecipitation of c-MYC with INI1.
Figure 4: Dominant-negative mutants of BRG1 and INI1 inhibit c-Myc-mediated transactivation.

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Acknowledgements

We thank V. Prasad, S. Goff, K. Calame, R. Kucherlapati, B. Morrow, J. Lenz, G. Childs and L. Zu for critically reading the manuscript; A. Morozov, K. Calame, L. Alland, R. DePinho, R. Eisenman, G. Crabtree, R. Pestell and L. Zhu for plasmids and reagents; and N. Schreiber-Agus and A. Skoultchi for useful discussions. This work was supported by grant AI39951 from NIH to G.V.K.

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Correspondence to Ganjam V. Kalpana.

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Cheng, SW., Davies, K., Yung, E. et al. c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function. Nat Genet 22, 102–105 (1999). https://doi.org/10.1038/8811

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