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Requirement for chromatin-remodeling complex in novel tumor suppressor HIC1-mediated transcriptional repression and growth control

Oncogene volume 28, pages 651–661 (2009)Cite this article

A Retraction to this article was published on 20 October 2011

Abstract

HIC1 is a newly discovered tumor suppressor and transcriptional repressor that is frequently silenced in human tumors. HIC1 protein expression has been linked to better outcomes in breast cancers. The molecular mechanism underlying HIC1-mediated transcriptional and growth suppression, and the relevant targets of HIC1-mediated transcriptional modulation, is currently unclear. We have identified an HIC1 DNA-binding site in E2F-responsive gene promoters and demonstrate that HIC1 targets E2F-responsive genes for transcriptional regulation and growth suppression. We and others have recently discovered that Brg1, a central component of the SWI/SNF chromatin-remodeling family, is required for the transcriptional regulation of multiple cell cycle control-related genes, including E2F-responsive promoters. We studied HIC1 interactions with, and dependence upon, Brg1 activity, and found that HIC1 can recruit Brg1 to E2F-responsive promoters and that its transcriptional repression of these genes is dependent upon Brg1. These data indicate that HIC1 is a central molecule in a novel mechanism controlling cell growth and that the disruption of this HIC1-mediated pathway may lead to abnormal cell proliferation and, ultimately, cancer.

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Acknowledgements

We thank Dr Srikumar P Chellappan for his continuous support. This study was partially supported by grants from Susan G Komen Breast Cancer Foundation Research Award (BCTR0403163) (SW) and the National Cancer Institute ((CA102940) (SW) and (CA101992) (DVF)) and by the Karin Grunebaum Cancer Research Foundation (DVF). SW is the recipient of DOD/CDMRP 2008 Breast Cancer Concept Award, Carter Family Foundation for Melanoma Research grant award, a BUSM Department of Medicine Pilot Project Grant Award and an Aid for Cancer Research grant award.

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Authors and Affiliations

  1. Cancer Research Center, Boston University School of Medicine, Boston, MA, USA

    B Zhang, K J Chambers, D V Faller & S Wang

  2. CNRS UMR 8161, Institut de, Biologie de Lille, Institut Pasteur de Lille, Lille Cedex, France

    D Leprince

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  1. B Zhang
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  2. K J Chambers
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  3. D Leprince
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  4. D V Faller
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  5. S Wang
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Correspondence to S Wang.

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Zhang, B., Chambers, K., Leprince, D. et al. Requirement for chromatin-remodeling complex in novel tumor suppressor HIC1-mediated transcriptional repression and growth control. Oncogene 28, 651–661 (2009). https://doi.org/10.1038/onc.2008.419

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Keywords

  • HIC1
  • E2F1
  • Brg1
  • SWI/SNF
  • transcription
  • cell cycle

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