Requirement for chromatin-remodeling complex in novel tumor suppressor hic1-mediated transcriptional repression and growth control

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. Access through your institution Buy or subscribe This is a

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INTO THE DUAL ROLE OF CCAR2/DBC1 IN CANCER Article Open access 01 August 2023 A MYC-ZNF148-ID1/3 REGULATORY AXIS MODULATING CANCER STEM CELL TRAITS IN AGGRESSIVE BREAST CANCER Article Open

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Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Cancer Research Center, Boston University School of Medicine, Boston, MA, USA B Zhang, K J Chambers, D V Faller & S

Wang * CNRS UMR 8161, Institut de, Biologie de Lille, Institut Pasteur de Lille, Lille Cedex, France D Leprince Authors * B Zhang View author publications You can also search for this author

inPubMed Google Scholar * K J Chambers View author publications You can also search for this author inPubMed Google Scholar * D Leprince View author publications You can also search for

this author inPubMed Google Scholar * D V Faller View author publications You can also search for this author inPubMed Google Scholar * S Wang View author publications You can also search

for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to S Wang. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 10 July 2008 * Revised: 19 September 2008 * Accepted: 10 October 2008 * Published: 17 November 2008 * Issue Date:

05 February 2009 * DOI: https://doi.org/10.1038/onc.2008.419 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * HIC1 * E2F1 * Brg1 * SWI/SNF *

transcription * cell cycle