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

Nature Genetics volume 22, pages 102–105 (1999)Cite this article

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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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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Authors and Affiliations

  1. Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave, U821, Bronx, New York, 10461, New York
    S.-W. Grace Cheng, Kelvin P. Davies, Eric Yung, Ralph J. Beltran & Ganjam V. Kalpana
  2. Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, 10032, New York, USA
    Jin Yu

Authors

  1. S.-W. Grace Cheng
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  2. Kelvin P. Davies
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  3. Eric Yung
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  4. Ralph J. Beltran
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  5. Jin Yu
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  6. Ganjam V. Kalpana
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Correspondence toGanjam 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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