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Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes

Oncogene volume 23, pages 3462–3473 (2004)Cite this article

Abstract

The INI1/hSNF5 tumor suppressor is an integral component of mammalian SWI/SNF chromatin remodeling enzymes that contain SNF2 family ATPases BRM (Brahma) or BRG1 (Brahma Related Gene 1) and that contribute to the regulation of many genes. Genetic studies of yeast SWI/SNF enzyme revealed similar phenotypes when single or multiple components of the enzyme were deleted, indicating a requirement for each subunit. To address the contribution of INI1 in the regulation of SWI/SNF-dependent genes in mammalian cells, we examined the expression of multiple BRG1-dependent, constitutively expressed genes in INI1-deficient cancer cell lines. At least one INI1-deficient line expressed each gene, and reintroduction of INI1 had negligible effects on expression levels. Lack of INI1 also did not prevent interferon gamma (IFNγ)-mediated induction of CIITA, which is BRG1 dependent, and GBP-1, which is BRG1 enhanced, and reintroduction of INI1 had minimal effects. Chromatin immunoprecipitation experiments revealed that BRG1 inducibly binds to the CIITA promoter despite the absence of INI1. Unlike yeast deleted for the INI1 homologue, SWI/SNF enzymes in INI1-deficient cells were largely intact. Thus in human cells, SWI/SNF enzyme complex formation and the expression of many BRG1-dependent genes are independent of INI1.

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Acknowledgements

We thank David Hill and Corey Smith for advice and help with the fractionation, George Witman for use of the Beckman Airfuge, Lisa Borghesi for the CD25 primers, Noel Buckley for providing pCS2(+), and Rod Bremner for advice and discussion. HeLa cell extracts utilized in Figure 8b were derived from HeLa cells grown by the National Cell Cuture Center. This work was supported by a grant from the NCI to SNJ and ANI, by a Scholar Award from the Leukemia and Lymphoma Society to ANI, and by grants from the Ellison Medical Foundation and the Rett Syndrome Research Foundation to WW.

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  1. Department of Cell Biology, University of Massachusetts Medical School, Worcester, 01655, MA, USA

    Diem N Doan, Timothy M Veal, Stephen N Jones & Anthony N Imbalzano

  2. Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, 21224, Maryland, USA

    Zhijiang Yan & Weidong Wang

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Correspondence to Anthony N Imbalzano.

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Doan, D., Veal, T., Yan, Z. et al. Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes. Oncogene 23, 3462–3473 (2004). https://doi.org/10.1038/sj.onc.1207472

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