Inhibition of cyclin D1 gene transcription by Brg-1

Rao, M. et al. (2008) Inhibition of cyclin D1 gene transcription by Brg-1. Cell Cycle, 7(5), pp. 647-655. (doi: 10.4161/cc.7.5.5446)

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The evolutionarily conserved SWI-SNF chromatin remodeling complex regulates cellular proliferation. A catalytic subunit, BRG-1, is frequently down regulated, silenced or mutated in malignant cells, however, the mechanism by which BRG-1 may function as a tumor suppressor or block breast cancer cellular proliferation is not understood. The cyclin D1 gene is a collaborative oncogene overexpressed in greater than 50% of human breast cancers. Herein, BRG-1 inhibited DNA synthesis and cyclin D1 expression in human MCF-7 breast cancer epithelial cells. The cyclin D1 promoter AP-1 and CRE sites were required for repression by BRG-1 in promoter assays. BRG-1 deficient cells abolished and siRNA to BRG-1 reduced, formation of the BRG-1 chromatin complex. The endogenous cyclin D1 promoter AP-1 site bound BRG-1. Estradiol treatment of MCF7 cells induced recruitment of BRG-1 to the endogenous hpS2 gene promoter. Estradiol, which induced cyclin D1 abundance, was associated with a reduction in recruitment of the co-repressors HP1α/HDAC1 to the endogenous cyclin D1 promoter AP-1/BRG-1 binding sites. These studies suggest the endogenous cyclin D1 promoter BRG-1 binding site functions as a molecular scaffold in the context of local chromatin upon which coactivators and corepressors are recruited to regulate cyclin D1.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Murphy, Professor Daniel
Authors: Rao, M., Casimiro, M.C., Lisanti, M.P., D'Amico, M., Wang, C., Shirley, L.A., Leader, J.E., Liu, M., Stallcup, M., Engel, D.A., Murphy, D.J., and Pestell, R.G.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cell Cycle
ISSN (Online):1551-4005

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