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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kadonaga, J.T. Eukaryotic transcription: an interlaced network of transcription factors and chromatin-modifying machines. Cell 92, 307 –313 (1998).
Workman, J.L. & Kingston, R.E. Alteration of nucleosome structure as a mechanism of transcriptional regulation. Annu. Rev. Biochem. 67, 545–579 ( 1998).
Cairns, B.R. Chromatin remodeling machines: similar motors, ulterior motives. Trends Biochem. Sci. 23, 20–25 (1998).
Kingston, R.E., Bunker, C.A. & Imbalzano, A.N. Repression and activation by multiprotein complexes that alter chromatin structure. Genes Dev. 10, 905–920 (1996).
Peterson, C.L. Multiple switches to turn on chromatin? Curr. Opin. Genet. Dev. 6, 171–175 ( 1996).
Dunaief, J.L. et al. The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest. Cell 79, 119 –130 (1994).
Shanahan, F., Seghezzi, W., Parry, D., Mahony, D. & Lees, E. Cyclin E associates with BAF155 and BRG1, components of the mammalian SWI-SNF complex, and alters the ability of BRG1 to induce growth arrest. Mol. Cell. Biol. 19, 1460– 1469 (1999).
Versteege, I. et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394, 203– 206 (1998).
Biegel, J. et al. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 59, 74– 79 (1999).
Fields, S. & Song, O.-K. A novel genetic system to detect protein-protein interactions. Nature 340, 245–246 (1989).
Young, K.H. Yeast two-hybrid: so many interactions, (in) so little time.... Biol. Reprod. 58, 301–311 (1998).
Facchini, L.M. & Penn, L.Z. The molecular role of Myc in growth and transformation: recent discoveries lead to new insights. FASEB J. 12, 633–651 (1998).
Henriksson, M. & Luscher, B. Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv. Cancer Res. 68, 109–182 (1996).
Morozov, A., Yung, E. & Kalpana, G. Structure-function analysis of integrase interactor 1/hSNF5L1 reveals differential properties of two repeat motifs present in the highly conserved region. Proc. Natl Acad. Sci. USA 95, 1120–1125 (1998).
Muchardt, C., Sardet, C., Bourachot, B., Onufryk, C. & Yaniv, M. A human protein with homology to Saccharomyces cerevisiae SNF5 interacts with the potential helicase hbrm. Nucleic Acids Res. 23, 1127–1132 (1995).
Rozenblatt-Rosen, O. et al. The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components fo the SWI/SNF complex. Proc. Natl Acad. Sci. USA 95, 4152– 4157 (1998).
Laherty, C.D., Yang, Y.M., Sun, J.M., Seto, E. & Eisenman, R.N. Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 89, 349–356 (1997).
Alland, L. et al. Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression. Nature 387, 49– 55 (1997).
Khavari, P.A., Peterson, C.L., Tamkun, J.W., Mendel, D.B. & Crabtree, G.R. BRG1 contains a conserved domain of the SWI2/SNF2 family necessary for normal mitotic growth and transcription. Nature 366, 170–174 (1993).
Wang, W. et al. Purification and biochemical heterogeneity of the mammalian SWI/SNF complex. EMBO J. 15, 5370– 5382 (1996).
Shrivastava, A. et al. Inhibition of transcription regulator Yin-Yang-1 by association with c-Myc. Science 262, 1889– 1892 (1993).
Kalpana, G.V., Marmon, S., Wang, W., Crabtree, G.R. & Goff, S.P. Binding and stimulation of HIV-1 integrase by a human homologue of yeast transcription factor SNF5. Science 266, 2002–2006 (1994).
Kato, G.J., Barrett, J., Villa-Garcia, M. & Dang, C.V. An amino terminal c-MYC domain required for neoplastic transformation activates transcription. Mol. Cell. Biol. 10, 5914 –5920 (1990).
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/8811
This article is cited by
-
cBAF complex components and MYC cooperate early in CD8+ T cell fate
Nature (2022)
-
MYC oncogene elicits tumorigenesis associated with embryonic, ribosomal biogenesis, and tissue-lineage dedifferentiation gene expression changes
Oncogene (2022)
-
INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication
Nature Communications (2021)
-
PHF10 subunit of PBAF complex mediates transcriptional activation by MYC
Oncogene (2021)
-
Multiple interactions of the oncoprotein transcription factor MYC with the SWI/SNF chromatin remodeler
Oncogene (2021)